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BioMed Research International
Volume 2015 (2015), Article ID 324915, 19 pages
http://dx.doi.org/10.1155/2015/324915
Review Article

The Dialogue of the Host-Parasite Relationship: Leishmania spp. and Trypanosoma cruzi Infection

1Laboratório de Bioquímica de Protozoários e Imunofisiologia do Exercício, Disciplina de Parasitologia, DMIP, FCM, Universidade do Estado do Rio de Janeiro, Avenida Professor Manuel de Abreu 444, Pavilhão Américo Piquet Carneiro, 5° andar, Vila Isabel, 20550-170 Rio de Janeiro, RJ, Brazil
2Programa de Pós Graduação em Microbiologia/FCM/UERJ, Avenida Professor Manuel de Abreu 444, Pavilhão Américo Piquet Carneiro, 3° andar, Vila Isabel, 20550-170 Rio de Janeiro, RJ, Brazil
3Programa de Pós Graduação em Fisiopatologia Clínica e Experimental/FCM/UERJ, Avenida Professor Manuel de Abreu 444, Pavilhão Américo Piquet Carneiro, 5° andar, Vila Isabel, 20550-170 Rio de Janeiro, RJ, Brazil
4Laboratório de Imunofarmacologia Parasitária, Disciplina de Parasitologia, DMIP, FCM, Universidade do Estado do Rio de Janeiro, Avenida Professor Manuel de Abreu 444, Pavilhão Américo Piquet Carneiro, 5° andar, Vila Isabel, 20550-170 Rio de Janeiro, RJ, Brazil

Received 27 June 2014; Revised 1 September 2014; Accepted 2 September 2014

Academic Editor: Miriam Rodriguez-Sosa

Copyright © 2015 Carlos Gustavo Vieira de Morais et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. A. Patz, T. K. Graczyk, N. Geller, and A. Y. Vittor, “Effects of environmental change on emerging parasitic diseases,” International Journal for Parasitology, vol. 30, no. 12-13, pp. 1395–1405, 2000. View at Publisher · View at Google Scholar · View at Scopus
  2. D. Butler, “Lost in translation,” Nature, vol. 449, no. 7159, pp. 158–159, 2007. View at Publisher · View at Google Scholar · View at Scopus
  3. R. Lainson, R. D. Ward, and J. J. Shaw, “Leishmania in phlebotomid sandflies: VI. Importance of hindgut development in distinguishing between parasites of the Leishmania mexicana and L. braziliensis complexes,” Proceedings of the Royal Society of London: Biological Sciences, vol. 199, no. 1135, pp. 309–320, 1977. View at Publisher · View at Google Scholar · View at Scopus
  4. R. Killick-Kendrick, “The biology and control of phlebotomine sand flies,” Clinics in Dermatology, vol. 17, no. 3, pp. 279–289, 1999. View at Publisher · View at Google Scholar · View at Scopus
  5. J. Alvar, I. D. Vélez, C. Bern et al., “Leishmaniasis worldwide and global estimates of its incidence,” PLoS ONE, vol. 7, no. 5, Article ID e35671, 2012. View at Publisher · View at Google Scholar · View at Scopus
  6. WHO, “Research priorities for chagas disease, human African trypanosomiasis and leishmaniasis,” Tech. Rep., TDR Disease Reference Group on Chagas Disease, 2012. View at Google Scholar
  7. R. da Silva and D. L. Sacks, “Metacyclogenesis is a major determinant of Leishmania promastigote virulence and attenuation,” Infection and Immunity, vol. 55, no. 11, pp. 2802–2806, 1987. View at Google Scholar · View at Scopus
  8. R. Zeledon, R. Bolanos, and M. Rojas, “Scanning electron microscopy of the final phase of the life cycle of Trypanosoma cruzi in the insect vector,” Acta Tropica, vol. 41, no. 1, pp. 39–43, 1984. View at Google Scholar · View at Scopus
  9. C. de Trez, S. Magez, S. Akira, B. Ryffel, Y. Carlier, and E. Muraille, “iNOS-producing inflammatory dendritic cells constitute the major infected cell type during the chronic Leishmania major infection phase of C57BL/6 resistant mice,” PLoS Pathogens, vol. 5, no. 6, Article ID e1000494, 2009. View at Publisher · View at Google Scholar · View at Scopus
  10. P. Kaye and P. Scott, “Leishmaniasis: complexity at the host-pathogen interface,” Nature Reviews Microbiology, vol. 9, no. 8, pp. 604–615, 2011. View at Publisher · View at Google Scholar · View at Scopus
  11. L. Beattie, A. Peltan, A. Maroof et al., “Dynamic imaging of experimental Leishmania donovani-induced hepatic granulomas detects kupffer cell-restricted antigen presentation to antigen-specific CD8+ T cells,” PLoS Pathogens, vol. 6, no. 3, Article ID e1000805, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. M. E. Bianchi, “DAMPs, PAMPs and alarmins: all we need to know about danger,” Journal of Leukocyte Biology, vol. 81, no. 1, pp. 1–5, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. R. D. Pearson and R. T. Steigbigel, “Phagocytosis and killing of the protozoan Leishmania donovani by human polymorphonuclear leukocytes,” Journal of Immunology, vol. 127, no. 4, pp. 1438–1443, 1981. View at Google Scholar · View at Scopus
  14. K. P. Chang, “Leishmanicidal mechanisms of human polymorphonuclear phagocytes,” The American Journal of Tropical Medicine and Hygiene, vol. 30, no. 2, pp. 322–333, 1981. View at Google Scholar · View at Scopus
  15. A. B. Guimarães-Costa, M. T. C. Nascimento, G. S. Froment et al., “Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 16, pp. 6748–6753, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. N. C. Peters, J. G. Egen, N. Secundino et al., “In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies,” Science, vol. 321, no. 5891, pp. 970–974, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. U. A. Wenzel, E. Bank, C. Florian et al., “Leishmania major parasite stage-dependent host cell invasion and immune evasion,” FASEB Journal, vol. 26, no. 1, pp. 29–39, 2012. View at Publisher · View at Google Scholar · View at Scopus
  18. M. A. Vannier-Santos, A. Martiny, and W. de Souza, “Cell biology of Leishmania spp.: invading and evading,” Current Pharmaceutical Design, vol. 8, no. 4, pp. 297–318, 2002. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Desjardins and A. Descoteaux, “Inhibition of phagolysosomal biogenesis by the Leishmania lipophosphoglycan,” Journal of Experimental Medicine, vol. 185, no. 12, pp. 2061–2068, 1997. View at Publisher · View at Google Scholar · View at Scopus
  20. A. Descoteaux and S. J. Turco, “Functional aspects of the Leishmania donovani lipophosphoglycan during macrophage infection,” Microbes and Infection, vol. 4, no. 9, pp. 975–981, 2002. View at Publisher · View at Google Scholar · View at Scopus
  21. E. Handman and J. W. Goding, “The Leishmania receptor for macrophages is a lipid-containing glycoconjugate,” EMBO Journal, vol. 4, no. 2, pp. 329–336, 1985. View at Google Scholar · View at Scopus
  22. P. Talamás-Rohana, S. D. Wright, M. R. Lennartz, and D. G. Russell, “Lipophosphoglycan from Leishmania mexicana promastigotes binds to members of the CR3, p150,95 and LFA-1 family of leukocyte integrins,” Journal of Immunology, vol. 144, no. 12, pp. 4817–4824, 1990. View at Google Scholar · View at Scopus
  23. A. Descoteaux, G. Matlashewski, and S. J. Turco, “Inhibition of macrophage protein kinase C-mediated protein phosphorylation by Leishmania donovani lipophosphoglycan,” The Journal of Immunology, vol. 149, no. 9, pp. 3008–3015, 1992. View at Google Scholar · View at Scopus
  24. Å. Holm, K. Tejle, T. Gunnarsson, K.-E. Magnusson, A. Descoteaux, and B. Rasmusson, “Role of protein kinase C α for uptake of unopsonized prey and phagosomal maturation in macrophages,” Biochemical and Biophysical Research Communications, vol. 302, no. 4, pp. 653–658, 2003. View at Publisher · View at Google Scholar · View at Scopus
  25. T. B. McNeely and S. J. Turco, “Requirement of lipophosphoglycan for intracellular survival of Leishmania donovani within human monocytes,” Journal of Immunology, vol. 144, no. 7, pp. 2745–2750, 1990. View at Google Scholar · View at Scopus
  26. G. F. Späth, L. A. Garraway, S. J. Turco, and S. M. Beverley, “The role(s) of lipophosphoglycan (LPG) in the establishment of Leishmania major infections in mammalian hosts,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 16, pp. 9536–9541, 2003. View at Publisher · View at Google Scholar · View at Scopus
  27. J. W. Booth, W. S. Trimble, and S. Grinstein, “Membrane dynamics in phagocytosis,” Seminars in Immunology, vol. 13, no. 6, pp. 357–364, 2001. View at Publisher · View at Google Scholar · View at Scopus
  28. D. J. Hackam, O. D. Rotstein, C. Sjolin, A. D. Schreiber, W. S. Trimble, and S. Grinstein, “v-SNARE-dependent secretion is required for phagocytosis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 20, pp. 11691–11696, 1998. View at Publisher · View at Google Scholar · View at Scopus
  29. K. K. Huynh, J. G. Kay, J. L. Stow, and S. Grinstein, “Fusion, fission, and secretion during phagocytosis,” Physiology, vol. 22, no. 6, pp. 366–372, 2007. View at Publisher · View at Google Scholar · View at Scopus
  30. L. Bajno, X.-R. Peng, A. D. Schreiber, H. P. Moore, W. S. Trimble, and S. Grinstein, “Focal exocytosis of VAMP3-containing vesicles at sites of phagosome formation,” Journal of Cell Biology, vol. 149, no. 3, pp. 697–706, 2000. View at Publisher · View at Google Scholar · View at Scopus
  31. V. Braun and F. Niedergang, “Linking exocytosis and endocytosis during phagocytosis,” Biology of the Cell, vol. 98, no. 3, pp. 195–201, 2006. View at Publisher · View at Google Scholar · View at Scopus
  32. D. Cox, D. J. Lee, B. M. Dale, J. Calafat, and S. Greenberg, “A Rab11-containing rapidly recycling compartment in macrophages that promotes phagocytosis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 2, pp. 680–685, 2000. View at Publisher · View at Google Scholar · View at Scopus
  33. M. Desjardins, “ER-mediated phagocytosis: a new membrane for new functions,” Nature Reviews Immunology, vol. 3, no. 4, pp. 280–291, 2003. View at Publisher · View at Google Scholar · View at Scopus
  34. K. Hatsuzawa, T. Tamura, H. Hashimoto et al., “Involvement of syntaxin 18, an endoplasmic reticulum (ER)-localized SNARE protein, in ER-mediated phagocytosis,” Molecular Biology of the Cell, vol. 17, no. 9, pp. 3964–3977, 2006. View at Publisher · View at Google Scholar · View at Scopus
  35. F. Niedergang, E. Colucci-Guyon, T. Dubois, G. Raposo, and P. Chavrier, “ADP ribosylation factor 6 is activated and controls membrane delivery during phagocytosis in macrophages,” The Journal of Cell Biology, vol. 161, no. 6, pp. 1143–1150, 2003. View at Publisher · View at Google Scholar · View at Scopus
  36. E. R. Chapman, “How does synaptotagmin trigger neurotransmitter release?” Annual Review of Biochemistry, vol. 77, pp. 615–641, 2008. View at Publisher · View at Google Scholar · View at Scopus
  37. R. Jahn, T. Lang, and T. C. Südhof, “Membrane fusion,” Cell, vol. 112, no. 4, pp. 519–533, 2003. View at Publisher · View at Google Scholar · View at Scopus
  38. I. Martinez, S. Chakrabarti, T. Hellevik, J. Morehead, K. Fowler, and N. W. Andrews, “Synaptotagmin VII regulates Ca2+-dependent exocytosis of lysosomes in fibroblasts,” Journal of Cell Biology, vol. 148, no. 6, pp. 1141–1149, 2000. View at Publisher · View at Google Scholar · View at Scopus
  39. C. Czibener, N. M. Sherer, S. M. Becker et al., “Ca2+ and synaptotagmin VII-dependent delivery of lysosomal membrane to nascent phagosomes,” Journal of Cell Biology, vol. 174, no. 7, pp. 997–1007, 2006. View at Publisher · View at Google Scholar · View at Scopus
  40. A. F. Vinet, M. Fukuda, and A. Descoteaux, “The exocytosis regulator synaptotagmin V controls phagocytosis in macrophages,” Journal of Immunology, vol. 181, no. 8, pp. 5289–5295, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. L. L. Vieira, N. Sacerdoti-Sierra, and C. L. Jaffe, “Effect of pH and temperature on protein kinase release by Leishmania donovani,” International Journal for Parasitology, vol. 32, no. 9, pp. 1085–1093, 2002. View at Publisher · View at Google Scholar · View at Scopus
  42. J.-F. Dermine, G. Goyette, M. Houde, S. J. Turco, and M. Desjardins, “Leishmania donovani lipophosphoglycan disrupts phagosome microdomains in J774 macrophages,” Cellular Microbiology, vol. 7, no. 9, pp. 1263–1270, 2005. View at Publisher · View at Google Scholar · View at Scopus
  43. M. E. Winberg, Å. Holm, E. Särndahl et al., “Leishmania donovani lipophosphoglycan inhibits phagosomal maturation via action on membrane rafts,” Microbes and Infection, vol. 11, no. 2, pp. 215–222, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. A. F. Vinet, M. Fukuda, S. J. Turco, and A. Descoteaux, “The Leishmania donovani lipophosphoglycan excludes the vesicular proton-ATPase from phagosomes by impairing the recruitment of Synaptotagmin V,” PLoS Pathogens, vol. 5, no. 10, Article ID e1000628, 2009. View at Publisher · View at Google Scholar · View at Scopus
  45. A. F. Vinet, S. Jananji, S. J. Turco, M. Fukuda, and A. Descoteaux, “Exclusion of synaptotagmin V at the phagocytic cup by Leishmania donovani lipophosphoglycan results in decreased promastigote internalization,” Microbiology, vol. 157, no. 9, pp. 2619–2628, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. B. A. P. Phan, M. A. Laflamme, A. Stempien-Otero, A. P. Limaye, F. S. Buckner, and W. C. Levy, “Confirmation of Chagas’ cardiomyopathy following heart transplantation,” Heart and Vessels, vol. 21, no. 5, pp. 325–327, 2006. View at Publisher · View at Google Scholar · View at Scopus
  47. R. Y. Dodd, E. P. Notari, and S. L. Stramer, “Current prevalence and incidence of infectious disease markers and estimated,” Transfusion, vol. 42, no. 8, pp. 975–979, 2002. View at Publisher · View at Google Scholar · View at Scopus
  48. G. Punukollu, R. M. Gowda, I. A. Khan, V. S. Navarro, and B. C. Vasavada, “Clinical aspects of the Chagas’ heart disease,” International Journal of Cardiology, vol. 115, no. 3, pp. 279–283, 2007. View at Publisher · View at Google Scholar · View at Scopus
  49. N. Yoshida, “Trypanosoma cruzi infection by oral route: how the interplay between parasite and host components modulates infectivity,” Parasitology International, vol. 57, no. 2, pp. 105–109, 2008. View at Publisher · View at Google Scholar · View at Scopus
  50. A. R. L. Teixeira, N. Nitz, M. C. Guimaro, C. Gomes, and C. A. Santos-Buch, “Chagas disease,” Postgraduate Medical Journal, vol. 82, no. 974, pp. 788–798, 2006. View at Publisher · View at Google Scholar · View at Scopus
  51. N. Yoshida, S. Favoreto Jr., A. T. Ferreira, and P. M. Manque, “Signal transduction induced in Trypanosoma cruzi metacyclic trypomastigotes during the invasion of mammalian cells,” Brazilian Journal of Medical and Biological Research, vol. 33, no. 3, pp. 269–278, 2000. View at Publisher · View at Google Scholar · View at Scopus
  52. S. N. J. Moreno and R. Docampo, “Calcium regulation in protozoan parasites,” Current Opinion in Microbiology, vol. 6, no. 4, pp. 359–364, 2003. View at Publisher · View at Google Scholar · View at Scopus
  53. N. W. Andrews, “Lysosomes and the plasma membrane: trypanosomes reveal a secret relationship,” Journal of Cell Biology, vol. 158, no. 3, pp. 389–394, 2002. View at Publisher · View at Google Scholar · View at Scopus
  54. M. C. Fernandes, A. R. Flannery, N. Andrews, and R. A. Mortara, “Extracellular amastigotes of Trypanosoma cruzi are potent inducers of phagocytosis in mammalian cells,” Cellular Microbiology, vol. 15, no. 6, pp. 977–991, 2013. View at Publisher · View at Google Scholar · View at Scopus
  55. B. A. Burleigh and A. M. Woolsey, “Cell signalling and Trypanosoma cruzi invasion,” Cellular Microbiology, vol. 4, no. 11, pp. 701–711, 2002. View at Publisher · View at Google Scholar · View at Scopus
  56. B. A. Burleigh, “Host cell signaling and Trypanosoma cruzi invasion: do all roads lead to lysosomes?” Science’s STKE, vol. 2005, article pe36, 2005. View at Google Scholar · View at Scopus
  57. N. Yoshida, “Molecular basis of mammalian cell invasion by Trypanosoma cruzi,” Anais da Academia Brasileira de Ciencias, vol. 78, no. 1, pp. 87–111, 2006. View at Google Scholar · View at Scopus
  58. E. V. Caler, S. Chakrabarti, K. T. Fowler, S. Rao, and N. W. Andrews, “The exocytosis-regulatory protein synaptotagmin VII mediates cell invasion by Trypanosoma cruzi,” Journal of Experimental Medicine, vol. 193, no. 9, pp. 1097–1104, 2001. View at Publisher · View at Google Scholar · View at Scopus
  59. K. L. Caradonna and B. A. Burleigh, “Mechanisms of host cell invasion by Trypanosoma cruzi,” Advances in Parasitology, vol. 76, pp. 33–61, 2011. View at Publisher · View at Google Scholar · View at Scopus
  60. A. O. Amer and M. S. Swanson, “A phagosome of one’s own: a microbial guide to life in the macrophage,” Current Opinion in Microbiology, vol. 5, no. 1, pp. 56–61, 2002. View at Publisher · View at Google Scholar · View at Scopus
  61. S. S. C. Rubin-de-Celis, H. Uemura, N. Yoshida, and S. Schenkman, “Expression of trypomastigote trans-sialidase in metacyclic forms of Trypanosoma cruzi increases parasite escape from its parasitophorous vacuole,” Cellular Microbiology, vol. 8, no. 12, pp. 1888–1898, 2006. View at Publisher · View at Google Scholar · View at Scopus
  62. J. Neres, R. A. Bryce, and K. T. Douglas, “Rational drug design in parasitology: trans-sialidase as a case study for Chagas disease,” Drug Discovery Today, vol. 13, no. 3-4, pp. 110–117, 2008. View at Publisher · View at Google Scholar · View at Scopus
  63. J. Neres, M. L. Brewer, L. Ratier et al., “Discovery of novel inhibitors of Trypanosoma cruzi trans-sialidase from in silico screening,” Bioorganic & Medicinal Chemistry Letters, vol. 19, no. 3, pp. 589–596, 2009. View at Publisher · View at Google Scholar · View at Scopus
  64. H. C. Barros, S. D. A. Silva et al., “Release of membrane-bound trails by Trypanosoma cruzi amastigotes onto modified surfaces and mammalian cells,” Journal of Eukaryotic Microbiology, vol. 43, no. 4, pp. 275–285, 1996. View at Publisher · View at Google Scholar · View at Scopus
  65. A. Acosta-Serrano, I. C. Almeida, L. H. Freitas-Junior, N. Yoshida, and S. Schenkman, “The mucin-like glycoprotein super-family of Trypanosoma cruzi: structure and biological roles,” Molecular and Biochemical Parasitology, vol. 114, no. 2, pp. 143–150, 2001. View at Publisher · View at Google Scholar · View at Scopus
  66. J. O. Previato, C. Jones, L. P. B. Gonçalves, R. Wait, L. R. Travassos, and L. Mendonça-Previato, “O-glycosidically linked N-acetylglucosamine-bound oligosaccharides from glycoproteins of Trypanosoma cruzi,” Biochemical Journal, vol. 301, part 1, pp. 151–159, 1994. View at Google Scholar · View at Scopus
  67. J. M. Di Noia, G. D. Pollevick, M. T. Xavier et al., “High diversity in mucin genes and mucin molecules in Trypanosoma cruzi,” The Journal of Biological Chemistry, vol. 271, no. 50, pp. 32078–32083, 1996. View at Publisher · View at Google Scholar · View at Scopus
  68. L. Mendonça-Previato, A. R. Todeschini, N. Heise, O. A. Agrellos, W. B. Dias, and J. O. Previato, “Chemical structure of major glycoconjugates from parasites,” Current Organic Chemistry, vol. 12, no. 11, pp. 926–939, 2008. View at Publisher · View at Google Scholar · View at Scopus
  69. J. O. Previato, A. F. B. Andrade, M. C. V. Pessolani, and L. Mendonca-Previato, “Incorporation of sialic acid into Trypanosoma cruzi macromolecules: a proposal for a new metabolic route,” Molecular and Biochemical Parasitology, vol. 16, no. 1, pp. 85–96, 1985. View at Publisher · View at Google Scholar · View at Scopus
  70. L. Mendonça-Previato, A. R. Todeschini, L. Freire de Lima, and J. O. Previato, “The trans-sialidase from Trypanosoma cruzi a putative target for Trypanocidal agents,” Open Parasitology Journal, vol. 4, no. 1, pp. 111–115, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. I. C. Almeida, M. A. J. Ferguson, S. Schenkman, and L. R. Travassos, “Lytic anti-α-galactosyl antibodies from patients with chronic Chagas’ disease recognize novel O-linked oligosaccharides on mucin-like glycosyl-phosphatidylinositol-anchored glycoproteins of Trypanosoma cruzi,” Biochemical Journal, vol. 304, no. 3, pp. 793–802, 1994. View at Google Scholar · View at Scopus
  72. S. Schenkman, M.-S. Jiang, G. W. Hart, and V. Nussenzweig, “A novel cell surface trans-sialidase of Trypanosoma cruzi generates a stage-specific epitope required for invasion of mammalian cells,” Cell, vol. 65, no. 7, pp. 1117–1125, 1991. View at Publisher · View at Google Scholar · View at Scopus
  73. R. A. Mortara, S. da Silva, M. F. Araguth, S. A. Blanco, and N. Yoshida, “Polymorphism of the 35- and 50-kilodalton surface glycoconjugates of Trypanosoma cruzi metacyclic trypomastigotes,” Infection and Immunity, vol. 60, no. 11, pp. 4673–4678, 1992. View at Google Scholar · View at Scopus
  74. C. Cortez, N. Yoshida, D. Bahia, and T. J. P. Sobreira, “Structural basis of the interaction of a Trypanosoma cruzi surface molecule implicated in oral infection with host cells and gastric mucin,” PLoS ONE, vol. 7, no. 7, Article ID e42153, 2012. View at Publisher · View at Google Scholar · View at Scopus
  75. M. M. Camargo, I. C. Almeida, M. E. S. Pereira, M. A. J. Ferguson, L. R. Travassos, and R. T. Gazzinelli, “Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi trypomastigotes initiate the synthesis of proinflammatory cytokines by macrophages,” The Journal of Immunology, vol. 158, no. 12, pp. 5890–5901, 1997. View at Google Scholar · View at Scopus
  76. F. Villalta, C. M. Smith, A. Ruiz-Ruano, and M. F. Lima, “A ligand that Trypanosoma cruzi uses to bind to mammalian cells to initiate infection,” FEBS Letters, vol. 505, no. 3, pp. 383–388, 2001. View at Publisher · View at Google Scholar · View at Scopus
  77. R. Giordano, R. Chammas, S. S. Veiga, W. Colli, and M. J. M. Alves, “An acidic component of the heterogeneous Tc-85 protein family from the surface of Trypanosoma cruzi is a laminin binding glycoprotein,” Molecular and Biochemical Parasitology, vol. 65, no. 1, pp. 85–94, 1994. View at Publisher · View at Google Scholar · View at Scopus
  78. M. H. Magdesian, R. R. Tonelli, M. R. Fessel et al., “A conserved domain of the gp85/trans-sialidase family activates host cell extracellular signal-regulated kinase and facilitates Trypanosoma cruzi infection,” Experimental Cell Research, vol. 313, no. 1, pp. 210–218, 2007. View at Publisher · View at Google Scholar · View at Scopus
  79. W. B. Dias, F. D. Fajardo, A. V. Graça-Souza et al., “Endothelial cell signalling induced by trans-sialidase from Trypanosoma cruzi,” Cellular Microbiology, vol. 10, no. 1, pp. 88–99, 2008. View at Publisher · View at Google Scholar · View at Scopus
  80. M. H. Magdesian, R. Giordano, H. Ulrich et al., “Infection by Trypanosoma cruzi: identification of a parasite ligand and its host cell receptor,” The Journal of Biological Chemistry, vol. 276, no. 22, pp. 19382–19389, 2001. View at Publisher · View at Google Scholar · View at Scopus
  81. N. Yoshida, S. A. Blanco, M. F. Araguth, and J. González, “The stage-specific 90-kilodalton surface antigen of metacyclic trypomastigotes of Trypanosoma cruzi,” Molecular and Biochemical Parasitology, vol. 39, no. 1, pp. 39–46, 1990. View at Publisher · View at Google Scholar · View at Scopus
  82. S. Schenkman, N. W. Andrews, V. Nussenzweig, and E. S. Robbins, “Trypanosoma cruzi invade a mammalian epithelial cell in a polarized manner,” Cell, vol. 55, no. 1, pp. 157–165, 1988. View at Publisher · View at Google Scholar · View at Scopus
  83. M. L. S. Guther, M. L. C. De Almeida, N. Yoshida, and M. A. J. Ferguson, “Structural studies on the glycosylphosphatidylinositol membrane anchor of Trypanosoma cruzi 1G7-antigen. The structure of the glycan core,” Journal of Biological Chemistry, vol. 267, no. 10, pp. 6820–6828, 1992. View at Google Scholar · View at Scopus
  84. J. Scharfstein, V. Schmitz, V. Morandi et al., “Host cell invasion by Trypanosoma cruzi is potentiated by activation of bradykinin B2 receptors,” Journal of Experimental Medicine, vol. 192, no. 9, pp. 1289–1300, 2000. View at Publisher · View at Google Scholar · View at Scopus
  85. A. C. M. Murta, P. M. Persechini, T. De Souto Padron, W. De Souza, J. A. Guimaraes, and J. Scharfstein, “Structural and functional identification of GP57/51 antigen of Trypanosoma cruzi as a cysteine proteinase,” Molecular and Biochemical Parasitology, vol. 43, no. 1, pp. 27–38, 1990. View at Publisher · View at Google Scholar · View at Scopus
  86. T. Souto-Padron, O. E. Campetella, J. J. Cazzulo, and W. de Souza, “Cysteine proteinase in Trypanosoma cruzi: immunocytochemical localization and involvement in parasite-host cell interaction,” Journal of Cell Science, vol. 96, part 3, pp. 485–490, 1990. View at Google Scholar · View at Scopus
  87. M. N. L. Meirelles, L. Juliano, E. Carmona et al., “Inhibitors of the major cysteinyl proteinase (GP57/51) impair host cell invasion and arrest the intracellular development of Trypanosoma cruzi in vitro,” Molecular and Biochemical Parasitology, vol. 52, no. 2, pp. 175–184, 1992. View at Publisher · View at Google Scholar · View at Scopus
  88. M. D. Hazenberg and H. Spits, “Human innate lymphoid cells,” Blood, vol. 124, no. 5, pp. 700–709, 2014. View at Publisher · View at Google Scholar
  89. H. Spits, D. Artis, M. Colonna et al., “Innate lymphoid cells-a proposal for uniform nomenclature,” Nature Reviews Immunology, vol. 13, no. 2, pp. 145–149, 2013. View at Publisher · View at Google Scholar · View at Scopus
  90. C. S. N. Klose, M. Flach, L. Möhle et al., “Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages,” Cell, vol. 157, no. 2, pp. 340–356, 2014. View at Publisher · View at Google Scholar · View at Scopus
  91. D. Schenten and R. Medzhitov, “The control of adaptive immune responses by the innate immune system,” Advances in Immunology, vol. 109, pp. 87–124, 2011. View at Publisher · View at Google Scholar · View at Scopus
  92. C. Olive, “Pattern recognition receptors: sentinels in innate immunity and targets of new vaccine adjuvants,” Expert Review of Vaccines, vol. 11, no. 2, pp. 237–256, 2012. View at Publisher · View at Google Scholar · View at Scopus
  93. R. Medzhitov and C. A. Janeway Jr., “Innate immune recognition and control of adaptive immune responses,” Seminars in Immunology, vol. 10, no. 5, pp. 351–353, 1998. View at Publisher · View at Google Scholar · View at Scopus
  94. A. Iwasaki and R. Medzhitov, “Regulation of adaptive immunity by the innate immune system,” Science, vol. 327, no. 5963, pp. 291–295, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. J. J. O’Shea and W. E. Paul, “Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells,” Science, vol. 327, no. 5969, pp. 1098–1102, 2010. View at Publisher · View at Google Scholar · View at Scopus
  96. J. E. Allen and R. M. Maizels, “Diversity and dialogue in immunity to helminths,” Nature Reviews Immunology, vol. 11, no. 6, pp. 375–388, 2011. View at Publisher · View at Google Scholar · View at Scopus
  97. B. Pulendran and D. Artis, “New paradigms in type 2 immunity,” Science, vol. 337, no. 6093, pp. 431–435, 2012. View at Publisher · View at Google Scholar · View at Scopus
  98. L. Y. Drake, K. Iijima, and H. Kita, “Group 2 innate lymphoid cells and CD4+ T cells cooperate to mediate type 2 immune response in mice,” Allergy, 2014. View at Publisher · View at Google Scholar
  99. A. Mizoguchi and A. K. Bhan, “A case for regulatory B cells,” Journal of Immunology, vol. 176, no. 2, pp. 705–710, 2006. View at Publisher · View at Google Scholar · View at Scopus
  100. D. J. Dilillo, T. Matsushita, and T. F. Tedder, “B10 cells and regulatory B cells balance immune responses during inflammation, autoimmunity, and cancer,” Annals of the New York Academy of Sciences, vol. 1183, pp. 38–57, 2010. View at Publisher · View at Google Scholar · View at Scopus
  101. D. A. A. Vignali, L. W. Collison, and C. J. Workman, “How regulatory T cells work,” Nature Reviews Immunology, vol. 8, no. 7, pp. 523–532, 2008. View at Publisher · View at Google Scholar · View at Scopus
  102. J. Banchereau, V. Pascual, and A. O’Garra, “From IL-2 to IL-37: the expanding spectrum of anti-inflammatory cytokines,” Nature Immunology, vol. 13, no. 10, pp. 925–931, 2012. View at Publisher · View at Google Scholar · View at Scopus
  103. D. McMahon-Pratt and J. Alexander, “Does the Leishmania major paradigm of pathogenesis and protection hold for New World cutaneous leishmaniases or the visceral disease?” Immunological Reviews, vol. 201, pp. 206–224, 2004. View at Publisher · View at Google Scholar · View at Scopus
  104. M. M. Kane and D. M. Mosser, “Leishmania parasites and their ploys to disrupt macrophage activation,” Current Opinion in Hematology, vol. 7, no. 1, pp. 26–31, 2000. View at Publisher · View at Google Scholar · View at Scopus
  105. J. A. D. O. Guerra, S. R. Prestes, H. Silveira et al., “Mucosal Leishmaniasis caused by Leishmania (Viannia) braziliensis and Leishmania (Viannia) guyanensis in the Brazilian Amazon,” PLoS Neglected Tropical Diseases, vol. 5, no. 3, p. e980, 2011. View at Publisher · View at Google Scholar · View at Scopus
  106. P. D. Marsden, “Mucosal leishmaniasis (“spundia” Escomel, 1911),” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 80, no. 6, pp. 859–876, 1986. View at Publisher · View at Google Scholar · View at Scopus
  107. C. Ronet, Y. Hauyon-La Torre, M. Revaz-Breton et al., “Regulatory B cells shape the development of Th2 immune responses in BALB/c mice infected with Leishmania major through IL-10 production,” Journal of Immunology, vol. 184, no. 2, pp. 886–894, 2010. View at Publisher · View at Google Scholar · View at Scopus
  108. A. Gomes-Silva, R. de Cássia Bittar, R. dos Santos Nogueira et al., “Can interferon-γ and interleukin-10 balance be associated with severity of human Leishmania (Viannia) braziliensis infection?” Clinical & Experimental Immunology, vol. 149, no. 3, pp. 440–444, 2007. View at Publisher · View at Google Scholar · View at Scopus
  109. P. I. Tarr, R. F. Aline Jr., B. L. Smiley, J. Scholler, J. Keithly, and K. Stuart, “LR1: a candidate RNA virus of Leishmania,” Proceedings of the National Academy of Sciences of the United States of America, vol. 85, no. 24, pp. 9572–9275, 1988. View at Publisher · View at Google Scholar · View at Scopus
  110. G. Widmer, A. M. Comeau, D. B. Furlong, D. F. Wirth, and J. L. Patterson, “Characterization of a RNA virus from the parasite Leishmania,” Proceedings of the National Academy of Sciences of the United States of America, vol. 86, no. 15, pp. 5979–5982, 1989. View at Publisher · View at Google Scholar · View at Scopus
  111. G. Salinas, M. Zamora, K. Stuart, and N. Saravia, “Leishmania RNA viruses in Leishmania of the Viannia subgenus,” The American Journal of Tropical Medicine and Hygiene, vol. 54, no. 4, pp. 425–429, 1996. View at Google Scholar · View at Scopus
  112. A. Ives, C. Ronet, F. Prevel et al., “Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis,” Science, vol. 331, no. 6018, pp. 775–778, 2011. View at Publisher · View at Google Scholar · View at Scopus
  113. C. Ronet, S. M. Beverley, and N. Fasel, “Muco-cutaneous leishmaniasis in the New World: the ultimate subversion,” Virulence, vol. 2, no. 6, pp. 547–552, 2011. View at Publisher · View at Google Scholar · View at Scopus
  114. M. Rayamajhi, J. Humann, S. Kearney, K. K. Hill, and L. L. Lenz, “Antagonistic crosstalk between type I and II interferons and increased host susceptibility to bacterial infections,” Virulence, vol. 1, no. 5, pp. 418–422, 2010. View at Publisher · View at Google Scholar · View at Scopus
  115. M.-A. Hartley, C. Ronet, H. Zangger, S. M. Beverley, and N. Fasel, “Leishmania RNA virus: when the host pays the toll,” Frontiers in Cellular and Infection Microbiology, vol. 2, p. 99, 2012. View at Google Scholar · View at Scopus
  116. C. M. V. Vendrame, L. D. Souza, M. D. T. Carvalho, K. Salgado, E. M. Carvalho, and H. Goto, “Insulin-like growth factor-I induced and constitutive arginase activity differs among isolates of Leishmania derived from patients with diverse clinical forms of Leishmania braziliensis infection,” Transactions of the Royal Society of Tropical Medicine and Hygiene, vol. 104, no. 8, pp. 566–568, 2010. View at Publisher · View at Google Scholar · View at Scopus
  117. H. E. Cummings, R. Tuladhar, and A. R. Satoskar, “Cytokines and their STATs in cutaneous and visceral leishmaniasis,” Journal of Biomedicine and Biotechnology, vol. 2010, Article ID 294389, 6 pages, 2010. View at Publisher · View at Google Scholar · View at Scopus
  118. J. Liese, U. Schleicher, and C. Bogdan, “The innate immune response against Leishmania parasites,” Immunobiology, vol. 213, no. 3-4, pp. 377–387, 2008. View at Publisher · View at Google Scholar · View at Scopus
  119. A. Bafica, H. C. Santiago, R. Goldszmid, C. Ropert, R. T. Gazzinelli, and A. Sher, “Cutting edge: TLR9 and TLR2 signaling together account for MyD88-dependent control of parasitemia in Trypanosoma cruzi infection,” Journal of Immunology, vol. 177, no. 6, pp. 3515–3519, 2006. View at Publisher · View at Google Scholar · View at Scopus
  120. R. Koga, S. Hamano, H. Kuwata et al., “TLR-dependent induction of IFN-β mediates host defense against Trypanosoma cruzi,” Journal of Immunology, vol. 177, no. 10, pp. 7059–7066, 2006. View at Publisher · View at Google Scholar · View at Scopus
  121. A. C. Monteiro, V. Schmitz, E. Svensjo et al., “Cooperative activation of TLR2 and bradykinin B2 receptor is required for induction of type 1 immunity in a mouse model of subcutaneous infection by Trypanosoma cruzi,” Journal of Immunology, vol. 177, no. 9, pp. 6325–6335, 2006. View at Publisher · View at Google Scholar · View at Scopus
  122. C. Bern, D. L. Martin, and R. H. Gilman, “Acute and congenital Chagas disease,” Advances in Parasitology, vol. 75, pp. 19–47, 2011. View at Publisher · View at Google Scholar · View at Scopus
  123. M. Samudio, S. Montenegro-James, M. Cabral, J. Martinez, A. R. De Arias, and M. A. James, “Cytokine responses in Trypanosoma cruzi-infected children in Paraguay,” The American Journal of Tropical Medicine and Hygiene, vol. 58, no. 1, pp. 119–121, 1998. View at Google Scholar · View at Scopus
  124. E. Moretti, B. Basso, L. Cervetta, A. Brigada, and G. Barbieri, “Patterns of cytokines and soluble cellular receptors in the sera of children with acute Chagas’ disease,” Clinical and Diagnostic Laboratory Immunology, vol. 9, no. 6, pp. 1324–1327, 2002. View at Publisher · View at Google Scholar · View at Scopus
  125. I. C. Almeida, M. M. Camargo, D. O. Procópio et al., “Highly purified glycosylphosphatidylinositols from Trypanosoma cruzi are potent proinflammatory agents,” EMBO Journal, vol. 19, no. 7, pp. 1476–1485, 2000. View at Publisher · View at Google Scholar · View at Scopus
  126. J. C. S. Aliberti, J. T. Souto, A. P. M. P. Marino et al., “Modulation of chemokine production and inflammatory responses in interferon-γ- and tumor necrosis factor-R1-deficient mice during Trypanosoma cruzi infection,” The American Journal of Pathology, vol. 158, no. 4, pp. 1433–1440, 2001. View at Publisher · View at Google Scholar · View at Scopus
  127. I. C. Almeida and R. T. Gazzinelli, “Proinflammatory activity of glycosylphosphatidylinositol anchors derived from Trypanosoma cruzi: structural and functional analyses,” Journal of Leukocyte Biology, vol. 70, no. 4, pp. 467–477, 2001. View at Google Scholar · View at Scopus
  128. I. A. Abrahamsohn and R. L. Coffman, “Trypanosoma cruzi: IL-10, TNF, IFN-γ and IL-12 regulate innate and acquired immunity to infection,” Experimental Parasitology, vol. 84, no. 2, pp. 231–244, 1996. View at Publisher · View at Google Scholar · View at Scopus
  129. M. S. Duthie and S. J. Kahn, “During acute Trypanosoma cruzi infection highly susceptible mice deficient in natural killer cells are protected by a single α-galactosylceramide treatment,” Immunology, vol. 119, no. 3, pp. 355–361, 2006. View at Publisher · View at Google Scholar · View at Scopus
  130. M. A. Muñoz-Fernández and M. Fresno, “Activation of human macrophages for the killing of intracellular Trypanosoma cruzi by TNF-α and IFN-γ through a nitric oxide-dependent mechanism,” Immunology Letters, vol. 33, no. 1, pp. 35–40, 1992. View at Publisher · View at Google Scholar · View at Scopus
  131. M. A. Muñoz-Fernández and M. Fresno, “Synergism between tumor necrosis factor-α and interferon-γ on macrophage activation for the killing of intracellular Trypanosoma cruzi through a nitric oxide-dependent mechanism,” European Journal of Immunology, vol. 22, no. 2, pp. 301–307, 1992. View at Publisher · View at Google Scholar · View at Scopus
  132. R. L. Cardoni, “La respuesta inflamatoria en la infección aguda con Trypanosoma cruzi,” Medicina, vol. 57, no. 2, pp. 227–234, 1997. View at Google Scholar · View at Scopus
  133. G. A. DosReis, “Cell-mediated immunity in experimental Trypanosoma cruzi infection,” Parasitology Today, vol. 13, no. 9, pp. 335–342, 1997. View at Publisher · View at Google Scholar · View at Scopus
  134. G. A. Martins, M. A. G. Cardoso, J. C. S. Aliberti, and J. S. Silva, “Nitric oxide-induced apoptotic cell death in the acute phase of Trypanosoma cruzi infection in mice,” Immunology Letters, vol. 63, no. 2, pp. 113–120, 1998. View at Publisher · View at Google Scholar · View at Scopus
  135. R. C. N. Melo, D. L. Fabrino, H. D’Ávila, H. C. Teixeira, and A. P. Ferreira, “Production of hydrogen peroxide by peripheral blood monocytes and specific macrophages during experimental infection with Trypanosoma cruzi in vivo,” Cell Biology International, vol. 27, no. 10, pp. 853–861, 2003. View at Publisher · View at Google Scholar · View at Scopus
  136. Y. Miyahira, “Trypanosoma cruzi infection from the view of CD8+ T cell immunity—an infection model for developing T cell vaccine,” Parasitology International, vol. 57, no. 1, pp. 38–48, 2008. View at Publisher · View at Google Scholar · View at Scopus
  137. A. M. Padilla, J. M. Bustamante, and R. L. Tarleton, “CD8+ T cells in Trypanosoma cruzi infection,” Current Opinion in Immunology, vol. 21, no. 4, pp. 385–390, 2009. View at Publisher · View at Google Scholar · View at Scopus
  138. C. Junqueira, B. Caetano, D. C. Bartholomeu et al., “The endless race between Trypanosoma cruzi and host immunity: lessons for and beyond Chagas disease,” Expert Reviews in Molecular Medicine, vol. 12, article e29, 2010. View at Publisher · View at Google Scholar · View at Scopus
  139. G. M. Krautz, J. C. Kissinger, and A. U. Krettli, “The targets of the lytic antibody response against Trypanosoma cruzi,” Parasitology Today, vol. 16, no. 1, pp. 31–34, 2000. View at Publisher · View at Google Scholar · View at Scopus
  140. W. O. Dutra, M. O. C. Rocha, and M. M. Teixeira, “The clinical immunology of human Chagas disease,” Trends in Parasitology, vol. 21, no. 12, pp. 581–587, 2005. View at Publisher · View at Google Scholar · View at Scopus
  141. F. F. de Araújo, R. Corrêa-Oliveira, M. O. C. Rocha et al., “Foxp3+ CD25high CD4+ regulatory T cells from indeterminate patients with Chagas disease can suppress the effector cells and cytokines and reveal altered correlations with disease severity,” Immunobiology, vol. 217, no. 8, pp. 768–777, 2012. View at Publisher · View at Google Scholar · View at Scopus
  142. A. M. C. Sartori, M. H. Lopes, B. Caramelli et al., “Simultaneous occurrence of acute myocarditis and reactivated Chagas’ disease in a patient with AIDS,” Clinical Infectious Diseases, vol. 21, no. 5, pp. 1297–1299, 1995. View at Publisher · View at Google Scholar · View at Scopus
  143. D. R. Almeida, A. C. Carvalho, J. N. Branco et al., “Chagas’ disease reactivation after heart transplantation: efficacy of allopurinol treatment,” The Journal of Heart and Lung Transplantation, vol. 15, no. 10, pp. 988–992, 1996. View at Google Scholar · View at Scopus
  144. R. L. Tarleton, M. J. Grusby, M. Postan, and L. H. Glimcher, “Trypanosoma cruzi infection in MHC-deficient mice: Further evidence for the role of both class I- and class II-restricted T cells in immune resistance and disease,” International Immunology, vol. 8, no. 1, pp. 13–22, 1996. View at Publisher · View at Google Scholar · View at Scopus
  145. B. Reina-San-Martín, A. Cosson, and P. Minoprio, “Lymphocyte polyclonal activation: a pitfall for vaccine design against infectious agents,” Parasitology Today, vol. 16, no. 2, pp. 62–67, 2000. View at Publisher · View at Google Scholar · View at Scopus
  146. B. Reina-San-Martín, W. Degrave, C. Rougeot et al., “A B-cell mitogen from a pathogenic trypanosome is a eukaryotic proline racemase,” Nature Medicine, vol. 6, no. 8, pp. 890–897, 2000. View at Publisher · View at Google Scholar · View at Scopus
  147. E. Ansa-Addo and J. Inal, “T. cruzi interference with host cell membrane integrity triggers the release of Plasma Membrane-derived Vesicles: a mechanism for entry into mammalian cells,” The Journal of Immunology, vol. 148, p. 5, 2010. View at Google Scholar
  148. S. Zambrano-Villa, D. Rosales-Borjas, J. C. Carrero, and L. Ortiz-Ortiz, “How protozoan parasites evade the immune response,” Trends in Parasitology, vol. 18, no. 6, pp. 272–278, 2002. View at Publisher · View at Google Scholar · View at Scopus
  149. I. Cestari, E. Ansa-Addo, P. Deolindo, J. M. Inal, and M. I. Ramirez, “Trypanosoma cruzi immune evasion mediated by host cell-derived microvesicles,” Journal of Immunology, vol. 188, no. 4, pp. 1942–1952, 2012. View at Publisher · View at Google Scholar · View at Scopus
  150. T. C. Araújo-Jorge, M. C. Waghabi, M. D. N. C. Soeiro, M. Keramidas, S. Bailly, and J.-J. Feige, “Pivotal role for TGF-β in infectious heart disease: the case of Trypanosoma cruzi infection and consequent Chagasic myocardiopathy,” Cytokine and Growth Factor Reviews, vol. 19, no. 5-6, pp. 405–413, 2008. View at Publisher · View at Google Scholar · View at Scopus
  151. M. Abu-Shakra, D. Buskila, and Y. Shoenfeld, “Molecular mimicry between host and pathogen: examples from parasites and implication,” Immunology Letters, vol. 67, no. 2, pp. 147–152, 1999. View at Publisher · View at Google Scholar · View at Scopus
  152. W. Savino, M. Do Carmo Leite-de-Moraes, M. Hontebeyrie-Joskowicz, and M. Dardenne, “Studies on the thymus in Chagas’ disease. I. Changes in the thymic microenvironment in mice acutely infected with Trypanosoma cruzi,” European Journal of Immunology, vol. 19, no. 9, pp. 1727–1733, 1989. View at Publisher · View at Google Scholar · View at Scopus
  153. A. F. F. R. Nardy, J. Luiz da Silva Filho, A. R. Pérez et al., “Trans-sialidase from Trypanosoma cruzi enhances the adhesion properties and fibronectin-driven migration of thymocytes,” Microbes and Infection, vol. 15, no. 5, pp. 365–374, 2013. View at Publisher · View at Google Scholar · View at Scopus
  154. Y. E. Latchman, S. C. Liang, Y. Wu et al., “PD-L1-deficient mice show that PD-L1 on T cells, antigen-presenting cells, and host tissues negatively regulates T cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 29, pp. 10691–10696, 2004. View at Publisher · View at Google Scholar · View at Scopus
  155. L. I. Terrazas, D. Montero, C. A. Terrazas, J. L. Reyes, and M. Rodríguez-Sosa, “Role of the programmed Death-1 pathway in the suppressive activity of alternatively activated macrophages in experimental cysticercosis,” International Journal for Parasitology, vol. 35, no. 13, pp. 1349–1358, 2005. View at Publisher · View at Google Scholar · View at Scopus
  156. L. R. Dulgerian, V. V. Garrido, C. C. Stempin, and F. M. Cerbán, “Programmed death ligand 2 regulates arginase induction and modifies Trypanosoma cruzi survival in macrophages during murine experimental infection,” Immunology, vol. 133, no. 1, pp. 29–40, 2011. View at Publisher · View at Google Scholar · View at Scopus
  157. H. D’Avila, C. G. Freire-de-Lima, N. R. Roque et al., “Host cell lipid bodies triggered by Trypanosoma cruzi infection and enhanced by the uptake of apoptotic cells are associated with prostaglandin E2 generation and increased parasite growth,” Journal of Infectious Diseases, vol. 204, no. 6, pp. 951–961, 2011. View at Publisher · View at Google Scholar · View at Scopus
  158. S. M. Puentes, R. P. Da Silva, D. L. Sacks, C. H. Hammer, and K. A. Joiner, “Serum resistance of metacyclic stage Leishmania major promastigotes is due to release of C5b-9,” The Journal of Immunology, vol. 145, no. 12, pp. 4311–4316, 1990. View at Google Scholar · View at Scopus
  159. T. Hermoso, Z. Fishelson, S. I. Becker, K. Hirschberg, and C. L. Jaffe, “Leishmanial protein kinases phosphorylate components of the complement system,” The EMBO Journal, vol. 10, no. 13, pp. 4061–4067, 1991. View at Google Scholar · View at Scopus
  160. A. Brittingham, C. J. Morrison, W. R. McMaster, B. S. McGwire, K.-P. Chang, and D. M. Mosser, “Role of the Leishmania surface protease gp63 in complement fixation, cell adhesion, and resistance to complement-mediated lysis,” Journal of Immunology, vol. 155, no. 6, pp. 3102–3111, 1995. View at Google Scholar · View at Scopus
  161. D. Sacks and A. Sher, “Evasion of innate immunity by parasitic protozoa,” Nature Immunology, vol. 3, no. 11, pp. 1041–1047, 2002. View at Publisher · View at Google Scholar · View at Scopus
  162. M. M. Kulkarni, W. R. McMaster, E. Kamysz, W. Kamysz, D. M. Engman, and B. S. McGwire, “The major surface-metalloprotease of the parasitic protozoan, Leishmania, protects against antimicrobial peptide-induced apoptotic killing,” Molecular Microbiology, vol. 62, no. 5, pp. 1484–1497, 2006. View at Publisher · View at Google Scholar · View at Scopus
  163. A. T. Remaley, D. B. Kuhns, R. E. Basford, R. H. Glew, and S. S. Kaplan, “Leishmanial phosphatase blocks neutrophil O2-production,” The Journal of Biological Chemistry, vol. 259, no. 18, pp. 11173–11175, 1984. View at Google Scholar · View at Scopus
  164. P. Gueirard, A. Laplante, C. Rondeau, G. Milon, and M. Desjardins, “Trafficking of Leishmania donovani promastigotes in non-lytic compartments in neutrophils enables the subsequent transfer of parasites to macrophages,” Cellular Microbiology, vol. 10, no. 1, pp. 100–111, 2008. View at Publisher · View at Google Scholar · View at Scopus
  165. A. S. A. Tuwaijri, I. A. A. Mofleh, and A. A. Mahmoud, “Effect of Leishmania major on human polymorphonuclear leucocyte function in vitro,” Journal of Medical Microbiology, vol. 32, no. 3, pp. 189–193, 1990. View at Publisher · View at Google Scholar · View at Scopus
  166. G. Van Zandbergen, N. Hermann, H. Laufs, W. Solbach, and T. Laskay, “Leishmania promastigotes release a granulocyte chemotactic factor and induce interleukin-8 release but inhibit gamma interferon-inducible protein 10 production by neutrophil granulocytes,” Infection and Immunity, vol. 70, no. 8, pp. 4177–4184, 2002. View at Publisher · View at Google Scholar · View at Scopus
  167. A. Wenzel and G. Van Zandbergen, “Lipoxin A4 receptor dependent leishmania infection,” Autoimmunity, vol. 42, no. 4, pp. 331–333, 2009. View at Publisher · View at Google Scholar · View at Scopus
  168. M. S. Faria, F. C. G. Reis, R. L. Azevedo-Pereira, L. S. Morrison, J. C. Mottram, and A. P. C. A. Lima, “Leishmania inhibitor of serine peptidase 2 prevents TLR4 activation by neutrophil elastase promoting parasite survival in murine macrophages,” The Journal of Immunology, vol. 186, no. 1, pp. 411–422, 2011. View at Publisher · View at Google Scholar · View at Scopus
  169. B. John and C. A. Hunter, “Immunology: neutrophil soldiers or Trojan horses?” Science, vol. 321, no. 5891, pp. 917–918, 2008. View at Publisher · View at Google Scholar · View at Scopus
  170. G. Van Zandbergen, A. Bollinger, A. Wenzel et al., “Leishmania disease development depends on the presence of apoptotic promastigotes in the virulent inoculum,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 37, pp. 13837–13842, 2006. View at Publisher · View at Google Scholar · View at Scopus
  171. R. M. Locksley, F. P. Heinzel, J. E. Fankhauser, C. S. Nelson, and M. D. Sadick, “Cutaneous host defense in leishmaniasis: Interaction of isolated dermal macrophages and epidermal Langerhans cells with the insect-stage promastigote,” Infection and Immunity, vol. 56, no. 2, pp. 336–342, 1988. View at Google Scholar · View at Scopus
  172. C. Bogdan, N. Donhauser, R. Döring, M. Röllinghoff, A. Diefenbach, and M. G. Rittig, “Fibroblasts as host cells in latent leishmaniosis,” Journal of Experimental Medicine, vol. 191, no. 12, pp. 2121–2129, 2000. View at Publisher · View at Google Scholar · View at Scopus
  173. C. Bogdan and M. Röllinghoff, “The immune response to Leishmania: mechanisms of parasite control and evasion,” International Journal for Parasitology, vol. 28, no. 1, pp. 121–134, 1998. View at Publisher · View at Google Scholar · View at Scopus
  174. A. Descoteaux and S. J. Turco, “Glycoconjugates in Leishmania infectivity,” Biochimica et Biophysica Acta, vol. 1455, no. 2-3, pp. 341–352, 1999. View at Publisher · View at Google Scholar · View at Scopus
  175. M. T. Shio, K. Hassani, A. Isnard et al., “Host cell signalling and leishmania mechanisms of evasion,” Journal of Tropical Medicine, vol. 2012, Article ID 819512, 14 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  176. C. Bogdan, M. Rollinghoff, and W. Solbach, “Evasion strategies of Leishmania parasites,” Parasitology Today, vol. 6, no. 6, pp. 183–187, 1990. View at Publisher · View at Google Scholar · View at Scopus
  177. M. A. Gomez, I. Contreras, M. Hallé, M. L. Tremblay, R. W. McMaster, and M. Olivier, “Leishmania GP63 alters host signaling through cleavage-activated protein tyrosine phosphatases,” Science Signaling, vol. 2, no. 90, p. ra58, 2009. View at Publisher · View at Google Scholar · View at Scopus
  178. S. Ghosh, S. Bhattacharyya, S. Das et al., “Generation of ceramide in murine macrophages infected with Leishmania donovani alters macrophage signaling events and aids intracellular parasitic survival,” Molecular and Cellular Biochemistry, vol. 223, no. 1-2, pp. 47–60, 2001. View at Publisher · View at Google Scholar · View at Scopus
  179. S. Ghosh, S. Bhattacharyya, M. Sirkar et al., “Leishmania donovani suppresses activated protein 1 and NF-κB activation in host macrophages via ceramide generation: involvement of extracellular signal-regulated kinase,” Infection and Immunity, vol. 70, no. 12, pp. 6828–6838, 2002. View at Publisher · View at Google Scholar · View at Scopus
  180. D. J. Gregory, M. Godbout, I. Contreras, G. Forget, and M. Olivier, “A novel form of NF-κB is induced by Leishmania infection: involvement in macrophage gene expression,” European Journal of Immunology, vol. 38, no. 4, pp. 1071–1081, 2008. View at Publisher · View at Google Scholar · View at Scopus
  181. B. M. Neves, R. Silvestre, M. Resende et al., “Activation of phosphatidylinositol 3-kinase/akt and impairment of nuclear factor-κB: Molecular mechanisms behind the arrested maturation/activation state of leishmania infantum-infected dendritic cells,” The American Journal of Pathology, vol. 177, no. 6, pp. 2898–2911, 2010. View at Publisher · View at Google Scholar · View at Scopus
  182. G. Forget, D. J. Gregory, and M. Olivier, “Proteasome-mediated degradation of STAT1α following infection of macrophages with Leishmania donovani,” The Journal of Biological Chemistry, vol. 280, no. 34, pp. 30542–30549, 2005. View at Publisher · View at Google Scholar · View at Scopus
  183. M. Olivier, D. J. Gregory, and G. Forget, “Subversion mechanisms by which Leishmania parasites can escape the host immune response: a signaling point of view,” Clinical Microbiology Reviews, vol. 18, no. 2, pp. 293–305, 2005. View at Publisher · View at Google Scholar · View at Scopus
  184. M. P. Barrett, J. C. Mottram, and G. H. Coombs, “Recent advances in identifying and validating drug targets in trypanosomes and leishmanias,” Trends in Microbiology, vol. 7, no. 2, pp. 82–88, 1999. View at Publisher · View at Google Scholar · View at Scopus
  185. S. H. Lee, J. L. Stephens, K. S. Paul, and P. T. Englund, “Fatty acid synthesis by elongases in trypanosomes,” Cell, vol. 126, no. 4, pp. 691–699, 2006. View at Publisher · View at Google Scholar · View at Scopus
  186. P. A. M. Michels, F. Bringaud, M. Herman, and V. Hannaert, “Metabolic functions of glycosomes in trypanosomatids,” Biochimica et Biophysica Acta, vol. 1763, no. 12, pp. 1463–1477, 2006. View at Publisher · View at Google Scholar · View at Scopus
  187. M. H. El Kouni, “Potential chemotherapeutic targets in the purine metabolism of parasites,” Pharmacology and Therapeutics, vol. 99, no. 3, pp. 283–309, 2003. View at Publisher · View at Google Scholar · View at Scopus
  188. S. Müller, E. Liebau, R. D. Walter, and R. L. Krauth-Siegel, “Thiol-based redox metabolism of protozoan parasites,” Trends in Parasitology, vol. 19, no. 7, pp. 320–328, 2003. View at Publisher · View at Google Scholar · View at Scopus
  189. T. C. Hammarton, J. Clark, F. Douglas, M. Boshart, and J. C. Mottram, “Stage-specific differences in cell cycle control in Trypanosoma brucei revealed by RNA interference of a mitotic cyclin,” The Journal of Biological Chemistry, vol. 278, no. 25, pp. 22877–22886, 2003. View at Publisher · View at Google Scholar · View at Scopus
  190. K. A. Werbovetz and R. E. Morgan, “Selective lead compounds against kinetoplastid tubulin,” Advances in Experimental Medicine and Biology, vol. 625, pp. 33–47, 2008. View at Publisher · View at Google Scholar · View at Scopus
  191. D. Savoia, T. Allice, and P.-A. Tovo, “Antileishmanial activity of HIV protease inhibitors,” International Journal of Antimicrobial Agents, vol. 26, no. 1, pp. 92–94, 2005. View at Publisher · View at Google Scholar · View at Scopus
  192. J. Nkemgu-Njinkeng, V. Rosenkranz, M. Wink, and D. Steverding, “Antitrypanosomal activities of proteasome inhibitors,” Antimicrobial Agents and Chemotherapy, vol. 46, no. 6, pp. 2038–2040, 2002. View at Publisher · View at Google Scholar · View at Scopus
  193. R. J. Glenn, A. J. Pemberton, H. J. Royle et al., “Trypanocidal effect of alpha′,beta′-epoxyketones indicates that trypanosomes are particularly sensitive to inhibitors of proteasome trypsin-like activity,” International Journal of Antimicrobial Agents, vol. 24, no. 3, pp. 286–289, 2004. View at Publisher · View at Google Scholar · View at Scopus
  194. S. R. Wilkinson, M. C. Taylor, D. Horn, J. M. Kelly, and I. Cheeseman, “A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 13, pp. 5022–5027, 2008. View at Publisher · View at Google Scholar · View at Scopus
  195. S. Patterson and S. Wyllie, “Nitro drugs for the treatment of trypanosomatid diseases: past, present, and future prospects,” Trends in Parasitology, vol. 30, no. 6, pp. 289–298, 2014. View at Publisher · View at Google Scholar · View at Scopus
  196. M. T. Bahia, I. M. de Andrade, T. A. F. Martins et al., “Fexinidazole: a potential new drug candidate for chagas disease,” PLoS Neglected Tropical Diseases, vol. 6, no. 11, Article ID e1870, 2012. View at Publisher · View at Google Scholar · View at Scopus
  197. M. T. Bahia, A. F. Nascimento, A. L. Mazzeti et al., “Antitrypanosomal activity of fexinidazole metabolites, potential new drug candidates for chagas disease,” Antimicrobial Agents and Chemotherapy, vol. 58, pp. 4362–4370, 2014. View at Publisher · View at Google Scholar
  198. Y. Zhou, N. Messier, M. Ouellette, B. P. Rosen, and R. Mukhopadhyay, “Leishmania major LmACR2 is a pentavalent antimony reductase that confers sensitivity to the drug Pentostam,” The Journal of Biological Chemistry, vol. 279, no. 36, pp. 37445–37451, 2004. View at Publisher · View at Google Scholar · View at Scopus
  199. V. S. Amato, F. F. Tuon, H. A. Bacha, V. A. Neto, and A. C. Nicodemo, “Mucosal leishmaniasis. Current scenario and prospects for treatment,” Acta Tropica, vol. 105, no. 1, pp. 1–9, 2008. View at Publisher · View at Google Scholar · View at Scopus
  200. J. Golenser and A. Domb, “New formulations and derivatives of amphotericin B for treatment of leishmaniasis,” Mini-Reviews in Medicinal Chemistry, vol. 6, no. 2, pp. 153–162, 2006. View at Publisher · View at Google Scholar · View at Scopus
  201. F. Chappuis, S. Sundar, A. Hailu et al., “Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?” Nature Reviews Microbiology, vol. 5, no. 11, pp. 873–882, 2007. View at Publisher · View at Google Scholar · View at Scopus
  202. P. Chugh, B. Bradel-Tretheway, C. M. R. Monteiro-Filho et al., “Akt inhibitors as an HIV-1 infected macrophage-specific anti-viral therapy,” Retrovirology, vol. 5, article 11, 2008. View at Publisher · View at Google Scholar · View at Scopus
  203. J. J. Berman, “Treatment of leishmaniasis with miltefosine: 2008 status,” Expert Opinion on Drug Metabolism and Toxicology, vol. 4, no. 9, pp. 1209–1216, 2008. View at Publisher · View at Google Scholar · View at Scopus
  204. T. Sun and Y. Zhang, “Pentamidine binds to tRNA through non-specific hydrophobic interactions and inhibits aminoacylation and translation,” Nucleic Acids Research, vol. 36, no. 5, pp. 1654–1664, 2008. View at Publisher · View at Google Scholar · View at Scopus
  205. B. Chawla, A. Jhingran, A. Panigrahi, K. D. Stuart, and R. Madhubala, “Paromomycin affects translation and vesicle-mediated trafficking as revealed by proteomics of paromomycin -susceptible -resistant leishmania donovani,” PLoS ONE, vol. 6, no. 10, Article ID e26660, 2011. View at Publisher · View at Google Scholar · View at Scopus
  206. J. Soto, J. Tolado, L. Valda et al., “Treatment of bolivian mucosal leishmaniasis with miltefosine,” Clinical Infectious Diseases, vol. 44, no. 3, pp. 350–356, 2007. View at Publisher · View at Google Scholar · View at Scopus
  207. M. Baginski and J. Czub, “Amphotericin B and its new derivatives—mode of action,” Current Drug Metabolism, vol. 10, no. 5, pp. 459–469, 2009. View at Publisher · View at Google Scholar · View at Scopus
  208. S. Sundar and J. Chakravarty, “Leishmaniasis: an update of current pharmacotherapy,” Expert Opinion on Pharmacotherapy, vol. 14, no. 1, pp. 53–63, 2013. View at Publisher · View at Google Scholar · View at Scopus
  209. S. Sundar, P. K. Sinha, S. A. Dixon et al., “Pharmacokinetics of oral sitamaquine taken with or without food and safety and efficacy for treatment of visceral leishmaniais: a randomized study in Bihar, India,” The American Journal of Tropical Medicine and Hygiene, vol. 84, no. 6, pp. 892–900, 2011. View at Publisher · View at Google Scholar · View at Scopus
  210. P. M. Loiseau, S. Cojean, and J. Schrével, “Sitamaquine as a putative antileishmanial drug candidate: from the mechanism of action to the risk of drug resistance,” Parasite, vol. 18, no. 2, pp. 115–119, 2011. View at Publisher · View at Google Scholar · View at Scopus
  211. J. A. Urbina, “Lipid biosynthesis pathways as chemotherapeutic targets in kinetoplastid parasites,” Parasitology, vol. 114, pp. S91–S99, 1997. View at Google Scholar · View at Scopus
  212. G. I. Lepesheva, F. Villalta, and M. R. Waterman, “Targeting Trypanosoma cruzi Sterol 14α-demethylase (CYP51),” Advances in Parasitology, vol. 75, pp. 65–87, 2011. View at Publisher · View at Google Scholar · View at Scopus
  213. W. de Souza and J. C. Rodrigues, “Sterol biosynthesis pathway as target for anti-trypanosomatid drugs,” Interdisciplinary Perspectives on Infectious Diseases, vol. 2009, Article ID 642502, 19 pages, 2009. View at Publisher · View at Google Scholar
  214. A. Khatami, A. Firooz, F. Gorouhi, and Y. Dowlati, “Treatment of acute Old World cutaneous leishmaniasis: a systematic review of the randomized controlled trials,” Journal of the American Academy of Dermatology, vol. 57, no. 2, pp. 335.e1–335.e29, 2007. View at Publisher · View at Google Scholar · View at Scopus
  215. R. Ramanathan, K. R. Talaat, D. P. Fedorko, S. Mahanty, and T. E. Nash, “A species-specific approach to the use of non-antimony treatments for cutaneous leishmaniasis,” The American Journal of Tropical Medicine and Hygiene, vol. 84, no. 1, pp. 109–117, 2011. View at Publisher · View at Google Scholar · View at Scopus
  216. A. Q. Sousa, M. S. Frutuoso, E. A. Moraes, R. D. Pearson, and M. M. L. Pompeu, “High-dose oral fluconazole therapy effective for cutaneous leishmaniasis due to leishmania (vianna) Braziliensis,” Clinical Infectious Diseases, vol. 53, no. 7, pp. 693–695, 2011. View at Publisher · View at Google Scholar · View at Scopus
  217. V. G. Duschak, “A decade of targets and patented drugs for chemotherapy of chagas disease,” Recent Patents on Anti-Infective Drug Discovery, vol. 6, no. 3, pp. 216–259, 2011. View at Publisher · View at Google Scholar · View at Scopus
  218. F. S. Buckner and J. A. Urbina, “Recent developments in sterol 14-demethylase inhibitors for Chagas disease,” International Journal for Parasitology: Drugs and Drug Resistance, vol. 2, pp. 236–242, 2012. View at Publisher · View at Google Scholar · View at Scopus
  219. I. Molina, J. Gómez I Prat, F. Salvador et al., “Randomized trial of posaconazole and benznidazole for chronic Chagas’ disease,” The New England Journal of Medicine, vol. 370, no. 20, pp. 1899–1908, 2014. View at Publisher · View at Google Scholar · View at Scopus
  220. N. Chamond, M. Goytia, N. Coatnoan et al., “Trypanosoma cruzi proline racemases are involved in parasite differentiation and infectivity,” Molecular Microbiology, vol. 58, no. 1, pp. 46–60, 2005. View at Publisher · View at Google Scholar · View at Scopus
  221. A. Berneman, L. Montout, S. Goyard et al., “Combined approaches for drug design points the way to novel proline racemase inhibitor candidates to fight chagas’ disease,” PLoS ONE, vol. 8, no. 4, Article ID e60955, 2013. View at Publisher · View at Google Scholar · View at Scopus
  222. E. Pozio, “Hiqhly active anti-retroviral therapy and opportunistic protozoan infections,” Parassitologia, vol. 46, no. 1-2, pp. 89–93, 2004. View at Google Scholar · View at Scopus
  223. G. Abbenante and D. P. Fairlie, “Protease inhibitors in the clinic,” Medicinal Chemistry, vol. 1, no. 1, pp. 71–104, 2005. View at Publisher · View at Google Scholar · View at Scopus
  224. L. O. Santos, B. S. Vitório, M. H. Branquinha, C. M. Pedroso e silva, A. L. S. Santos, and C. M. D’avila-Levy, “Nelfinavir is effective in inhibiting the multiplication and aspartic peptidase activity of Leishmania species, including strains obtained from HIV-positive patients,” Journal of Antimicrobial Chemotherapy, vol. 68, no. 2, Article ID dks410, pp. 348–353, 2013. View at Publisher · View at Google Scholar · View at Scopus
  225. L. O. Santos, A. S. Garcia-Gomes, M. Catanho et al., “Aspartic peptidases of human pathogenic trypanosomatids: perspectives and trends for chemotherapy,” Current Medicinal Chemistry, vol. 20, no. 25, pp. 3116–3133, 2013. View at Publisher · View at Google Scholar · View at Scopus
  226. S. L. Croft, S. Sundar, and A. H. Fairlamb, “Drug resistance in leishmaniasis,” Clinical Microbiology Reviews, vol. 19, no. 1, pp. 111–126, 2006. View at Publisher · View at Google Scholar · View at Scopus
  227. A. Martinelli, R. Moreira, and P. V. L. Cravo, “Malaria combination therapies: advantages and shortcomings,” Mini-Reviews in Medicinal Chemistry, vol. 8, no. 3, pp. 201–212, 2008. View at Publisher · View at Google Scholar · View at Scopus
  228. L. L. Silver, “Multi-targeting by monotherapeutic antibacterials,” Nature Reviews Drug Discovery, vol. 6, no. 1, pp. 41–55, 2007. View at Publisher · View at Google Scholar · View at Scopus
  229. A. Petrelli and S. Giordano, “From single- to multi-target drugs in cancer therapy: when aspecificity becomes an advantage,” Current Medicinal Chemistry, vol. 15, no. 5, pp. 422–432, 2008. View at Publisher · View at Google Scholar · View at Scopus
  230. B. M. Roatt, R. D. Aguiar-Soares, W. Coura-Vital et al., “Immunotherapy and immunochemotherapy in visceral leishmaniasis: promising treatments for this neglected disease,” Frontiers in Immunology, vol. 5, p. 272, 2014. View at Google Scholar
  231. J. Joshi, N. Malla, and S. Kaur, “A comparative evaluation of efficacy of chemotherapy, immunotherapy and immunochemotherapy in visceral leishmaniasis-an experimental study,” Parasitology International, vol. 63, no. 4, pp. 612–620, 2014. View at Publisher · View at Google Scholar · View at Scopus
  232. B. Monge-Maillo and R. López-Vélez, “Therapeutic options for old world cutaneous leishmaniasis and new world cutaneous and mucocutaneous leishmaniasis,” Drugs, vol. 73, no. 17, pp. 1889–1920, 2013. View at Publisher · View at Google Scholar · View at Scopus
  233. A. Khamesipour, “Therapeutic vaccines for leishmaniasis,” Expert Opinion on Biological Therapy, vol. 31, pp. 1–9, 2014. View at Publisher · View at Google Scholar