Table of Contents Author Guidelines Submit a Manuscript
Journal of Immunology Research
Volume 2018, Article ID 8695157, 14 pages
https://doi.org/10.1155/2018/8695157
Review Article

Receptors That Inhibit Macrophage Activation: Mechanisms and Signals of Regulation and Tolerance

Laboratorio de Inmunología Integrativa, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Ciudad de México, Mexico

Correspondence should be addressed to Isabel Sada-Ovalle; moc.liamg@xmadasi

Received 26 July 2017; Revised 7 November 2017; Accepted 20 November 2017; Published 11 February 2018

Academic Editor: Kebin Hu

Copyright © 2018 Ranferi Ocaña-Guzman 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. S. Wood, V. Jayaraman, E. J. Huelsmann et al., “Pro-inflammatory chemokine CCL2 (MCP-1) promotes healing in diabetic wounds by restoring the macrophage response,” PLoS One, vol. 9, no. 3, article e91574, 2014. View at Publisher · View at Google Scholar · View at Scopus
  2. S. Singh, H. Barr, Y. C. Liu et al., “Granulocyte-macrophage colony stimulatory factor enhances the pro-inflammatory response of interferon-γ-treated macrophages to Pseudomonas aeruginosa infection,” PLoS One, vol. 10, no. 2, article e0117447, 2015. View at Publisher · View at Google Scholar · View at Scopus
  3. S. Gordon, “Phagocytosis: an immunobiologic process,” Immunity, vol. 44, no. 3, pp. 463–475, 2016. View at Publisher · View at Google Scholar · View at Scopus
  4. F. Ginhoux and M. Guilliams, “Tissue-resident macrophage ontogeny and homeostasis,” Immunity, vol. 44, no. 3, pp. 439–449, 2016. View at Publisher · View at Google Scholar · View at Scopus
  5. D. Hashimoto, A. Chow, C. Noizat et al., “Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes,” Immunity, vol. 38, no. 4, pp. 792–804, 2013. View at Publisher · View at Google Scholar · View at Scopus
  6. S. Gordon and A. Plüddemann, “Tissue macrophages : heterogeneity and functions,” BMC Biology, vol. 15, no. 1, pp. 53–18, 2017. View at Publisher · View at Google Scholar
  7. S. Gordon, “Alternative activation of macrophages,” Nature Reviews Immunology, vol. 3, no. 1, pp. 23–35, 2003. View at Publisher · View at Google Scholar · View at Scopus
  8. F. O. Martinez and S. Gordon, “The M1 and M2 paradigm of macrophage activation : time for reassessment,” F1000Prime Reports, vol. 6, pp. 1–13, 2014. View at Publisher · View at Google Scholar · View at Scopus
  9. N. A. Gonzalez, J. A. Quintana, S. García-Silva et al., “Phagocytosis imprints heterogeneity in tissue-resident macrophages,” Journal of Experimental Medicine, vol. 214, no. 5, pp. 1281–1296, 2017. View at Publisher · View at Google Scholar
  10. Q. He, J. Johnston, and J. Zeitlinger, “ChIP-nexus enables improved detection of in vivo transcription factor binding footprints,” Nature Biotechnology, vol. 33, no. 4, pp. 395–401, 2015. View at Publisher · View at Google Scholar · View at Scopus
  11. T. Kimura, H. Sakamoto, E. Appella, and R. P. Siraganian, “Conformational changes induced in the protein tyrosine kinase p72syk by tyrosine phosphorylation or by binding of phosphorylated immunoreceptor tyrosine-based activation motif peptides,” Molecular and Cellular Biology, vol. 16, no. 4, pp. 1471–1478, 1996. View at Publisher · View at Google Scholar
  12. L. B. Ivashkiv, “Cross-regulation of signaling by ITAM-associated receptors,” Nature Immunology, vol. 10, no. 4, pp. 340–347, 2009. View at Publisher · View at Google Scholar · View at Scopus
  13. H. Schneider, K. V. Prasad, S. E. Shoelson, and C. E. Rudd, “CTLA-4 binding to the lipid kinase phosphatidylinositol 3-kinase in T cells,” Journal of Experimental Medicine, vol. 181, no. 1, pp. 351–355, 1995. View at Publisher · View at Google Scholar · View at Scopus
  14. F. M. Karlhofer, R. K. Ribaudo, and W. M. Yokoyama, “MHC class I alloantigen specificity of Ly-49+ IL-2-activated natural killer cells,” Nature, vol. 358, no. 6381, pp. 66–70, 1992. View at Publisher · View at Google Scholar
  15. Y. Zhu, S. Yao, and L. Chen, “Cell surface signaling molecules in the control of immune responses: a tide model,” Immunity, vol. 34, no. 4, pp. 466–478, 2011. View at Publisher · View at Google Scholar · View at Scopus
  16. E. O. Long, “Regulation of immune responses through inhibitory receptors,” Annual Review of Immunology, vol. 17, no. 1, pp. 875–904, 1999. View at Publisher · View at Google Scholar · View at Scopus
  17. T. Muta, T. Kurosaki, Z. Misulovin, M. Sanchez, M. C. Nussenzweig, and J. V. Ravetch, “A 13-amino-acid motif in the cytoplasmic domain of FcγRIIB modulates B-cell receptor signalling,” Nature, vol. 368, no. 6466, pp. 70–73, 1994. View at Publisher · View at Google Scholar
  18. P. Bruhns, F. Vély, O. Malbec, W. H. Fridman, E. Vivier, and M. Daëron, “Molecular basis of the recruitment of the SH2 domain-containing inositol 5-phosphatases SHIP1 and SHIP2 by FcγRIIB,” The Journal of Biological Chemistry, vol. 275, no. 48, pp. 37357–37364, 2000. View at Publisher · View at Google Scholar · View at Scopus
  19. S. A. Fuertes Marraco, N. J. Neubert, G. Verdeil, and D. E. Speiser, “Inhibitory receptors beyond T cell exhaustion,” Frontiers in Immunology, vol. 6, pp. 1–14, 2015. View at Publisher · View at Google Scholar · View at Scopus
  20. A. Maeda, M. Kurosaki, M. Ono, T. Takai, and T. Kurosaki, “Requirement of SH2-containing protein tyrosine phosphatases SHP-1 and SHP-2 for paired immunoglobulin-like receptor B (PIR-B)–mediated inhibitory signal,” The Journal of Experimental Medicine, vol. 187, no. 8, pp. 1355–1360, 1998. View at Publisher · View at Google Scholar · View at Scopus
  21. P. M. Odorizzi and E. J. Wherry, “Inhibitory receptors on lymphocytes: insights from infections,” The Journal of Immunology, vol. 188, no. 7, pp. 2957–2965, 2012. View at Publisher · View at Google Scholar · View at Scopus
  22. M. J. Butte, M. E. Keir, T. B. Phamduy, A. H. Sharpe, and G. J. Freeman, “PD-L1 interacts specifically with B7-1 to inhibit T cell proliferation,” Immunity, vol. 27, no. 1, pp. 111–122, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. J. G. Egen, M. S. Kuhns, and J. P. Allison, “CTLA-4: new insights into its biological function and use in tumor immunotherapy,” Nature Immunology, vol. 3, no. 7, pp. 611–618, 2002. View at Publisher · View at Google Scholar · View at Scopus
  24. E. O. Long, “Negative signaling by inhibitory receptors: the NK cell paradigm,” Immunological Reviews, vol. 224, no. 1, pp. 70–84, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. J. M. Moser, J. Gibbs, P. E. Jensen, and A. E. Lukacher, “CD94-NKG2A receptors regulate antiviral CD8+ T cell responses,” Nature Immunology, vol. 3, no. 2, pp. 189–195, 2002. View at Publisher · View at Google Scholar · View at Scopus
  26. G. G. Lin and J. G. Scott, “Investigations of the constitutive overexpression of CYP6D1 in the permethrin resistantLPR strain of house fly (Musca domestica),” Pesticide Biochemistry and Physiology, vol. 100, no. 2, pp. 130–134, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. Y. Ishida, Y. Agata, K. Shibahara, and T. Honjo, “Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death,” The EMBO Journal, vol. 11, no. 11, pp. 3887–3895, 1992. View at Google Scholar
  28. H. Dong, G. Zhu, K. Tamada, and L. Chen, “B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion,” Nature Medicine, vol. 5, no. 12, pp. 1365–1369, 1999. View at Publisher · View at Google Scholar · View at Scopus
  29. Y. Latchman, C. R. Wood, T. Chernova et al., “PD-L2 is a second ligand for PD-1 and inhibits T cell activation,” Nature Immunology, vol. 2, no. 3, pp. 261–268, 2001. View at Publisher · View at Google Scholar · View at Scopus
  30. H. Jin, A. C. Anderson, W. G. Tan et al., “Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 33, pp. 14733–14738, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. K. Sakuishi, L. Apetoh, J. M. Sullivan, B. R. Blazar, V. K. Kuchroo, and A. C. Anderson, “Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity,” The Journal of Experimental Medicine, vol. 207, no. 10, pp. 2187–2194, 2010. View at Publisher · View at Google Scholar · View at Scopus
  32. J. R. Brahmer, C. G. Drake, I. Wollner et al., “Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates,” Journal of Clinical Oncology, vol. 28, no. 19, pp. 3167–3175, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. D. M. Benson, C. E. Bakan, A. Mishra et al., “The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody,” Blood, vol. 116, no. 13, pp. 2286–2294, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. O. Hamid, C. Robert, A. Daud et al., “Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma,” The New England Journal of Medicine, vol. 369, no. 2, pp. 134–144, 2013. View at Publisher · View at Google Scholar · View at Scopus
  35. C. J. Ma, L. Ni, Y. Zhang et al., “PD-1 negatively regulates interleukin-12 expression by limiting STAT-1 phosphorylation in monocytes/macrophages duringchronic hepatitis C virus infection,” Immunology, vol. 132, no. 3, pp. 421–431, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. H. Y. Cho, E. K. Choi, S. W. Lee et al., “Programmed death-1 receptor negatively regulates LPS-mediated IL-12 production and differentiation of murine macrophage RAW264.7 cells,” Immunology Letters, vol. 127, no. 1, pp. 39–47, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. Y. Zhang, C. J. Ma, J. M. Wang et al., “Tim-3 negatively regulates IL-12 expression by monocytes in HCV infection,” PLoS One, vol. 6, no. 5, article e19664, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. Z. N. Zhang, M. L. Zhu, Y. H. Chen et al., “Elevation of Tim-3 and PD-1 expression on T cells appears early in HIV infection, and differential Tim-3 and PD-1 expression patterns can be induced by common γ-chain cytokines,” BioMed Research International, vol. 2015, Article ID 916936, 11 pages, 2015. View at Publisher · View at Google Scholar · View at Scopus
  39. S. R. Gordon, R. L. Maute, B. W. Dulken et al., “PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity,” Nature, vol. 545, no. 7655, pp. 495–499, 2017. View at Publisher · View at Google Scholar · View at Scopus
  40. S. M. Ansell, A. M. Lesokhin, I. Borrello et al., “PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma,” The New England Journal of Medicine, vol. 372, no. 4, pp. 311–319, 2015. View at Publisher · View at Google Scholar · View at Scopus
  41. Q. X. Qu, Q. Huang, Y. Shen, Y. B. Zhu, and X. G. Zhang, “The increase of circulating PD-L1-expressing CD68+ macrophage in ovarian cancer,” Tumor Biology, vol. 37, no. 4, pp. 5031–5037, 2016. View at Publisher · View at Google Scholar · View at Scopus
  42. S. R. Dannenmann, J. Thielicke, M. Stöckli et al., “Tumor-associated macrophages subvert T-cell function and correlate with reduced survival in clear cell renal cell carcinoma,” OncoImmunology, vol. 2, no. 3, article e23562, 2013. View at Publisher · View at Google Scholar · View at Scopus
  43. L. Monney, C. A. Sabatos, J. L. Gaglia et al., “Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease,” Nature, vol. 415, no. 6871, pp. 536–541, 2002. View at Publisher · View at Google Scholar · View at Scopus
  44. S. Chiba, M. Baghdadi, H. Akiba et al., “Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1,” Nature Immunology, vol. 13, no. 9, pp. 832–842, 2012. View at Publisher · View at Google Scholar · View at Scopus
  45. Y. Shang, Z. Li, H. Li, H. Xia, and Z. Lin, “TIM-3 expression in human osteosarcoma: correlation with the expression of epithelial-mesenchymal transition-specific biomarkers,” Oncology Letters, vol. 6, no. 2, pp. 490–494, 2013. View at Publisher · View at Google Scholar · View at Scopus
  46. T. Kadowaki, T. Arikawa, R. Shinonaga et al., “Galectin-9 signaling prolongs survival in murine lung-cancer by inducing macrophages to differentiate into plasmacytoid dendritic cell-like macrophages,” Clinical Immunology, vol. 142, no. 3, pp. 296–307, 2012. View at Publisher · View at Google Scholar · View at Scopus
  47. Y. Cao, X. Zhou, X. Huang et al., “Tim-3 expression in cervical cancer promotes tumor metastasis,” PLoS One, vol. 8, no. 1, article e53834, 2013. View at Publisher · View at Google Scholar · View at Scopus
  48. C. J. Ma, G. Y. Li, Y. Q. Cheng et al., “Cis association of galectin-9 with Tim-3 differentially regulates IL-12/IL-23 expressions in monocytes via TLR signaling,” PLoS One, vol. 8, no. 8, pp. e72488–e72415, 2013. View at Publisher · View at Google Scholar · View at Scopus
  49. R. H. DeKruyff, X. Bu, A. Ballesteros et al., “T cell/transmembrane, Ig, and mucin-3 allelic variants differentially recognize phosphatidylserine and mediate phagocytosis of apoptotic cells,” The Journal of Immunology, vol. 184, no. 4, pp. 1918–1930, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. M. J. Lee, Y. M. Heo, S. Hong, K. Kim, and S. Park, “The binding properties of glycosylated and non-glycosylated Tim-3 molecules on CD4+CD25+ T cells,” Immune Network, vol. 9, no. 2, pp. 58–63, 2009. View at Publisher · View at Google Scholar
  51. J. Lee, E. W. Su, C. Zhu et al., “Phosphotyrosine-dependent coupling of tim-3 to T-cell receptor signaling pathways,” Molecular and Cellular Biology, vol. 31, no. 19, pp. 3963–3974, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. A. M. deCathelineau and P. M. Henson, “The final step in programmed cell death: phagocytes carry apoptotic cells to the grave,” Essays in Biochemistry, vol. 39, pp. 105–117, 2003. View at Publisher · View at Google Scholar
  53. N. Kobayashi, P. Karisola, V. Peña-Cruz et al., “TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells,” Immunity, vol. 27, no. 6, pp. 927–940, 2007. View at Publisher · View at Google Scholar · View at Scopus
  54. E. Cao, X. Zang, U. A. Ramagopal et al., “T cell immunoglobulin mucin-3 crystal structure reveals a Galectin-9-independent ligand-binding surface,” Immunity, vol. 26, no. 3, pp. 311–321, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. M. Nakayama, H. Akiba, K. Takeda et al., “Tim-3 mediates phagocytosis of apoptotic cells and cross-presentation,” Blood, vol. 113, no. 16, pp. 3821–3830, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. K. Asano, M. Miwa, K. Miwa et al., “Masking of phosphatidylserine inhibits apoptotic cell engulfment and induces autoantibody production in mice,” The Journal of Experimental Medicine, vol. 200, no. 4, pp. 459–467, 2004. View at Publisher · View at Google Scholar · View at Scopus
  57. C. Zhu, A. C. Anderson, A. Schubart et al., “The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity,” Nature Immunology, vol. 6, no. 12, pp. 1245–1252, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. L. Golden-Mason, B. E. Palmer, N. Kassam et al., “Negative immune regulator Tim-3 is overexpressed on T cells in hepatitis C virus infection and its blockade rescues dysfunctional CD4+ and CD8+ T cells,” Journal of Virology, vol. 83, no. 18, pp. 9122–9130, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. J. S. Bezbradica and K. Schroder, “TRAF6 is a nexus for TLR-STAT1 crosstalk,” Immunology and Cell Biology, vol. 92, no. 9, pp. 737-738, 2014. View at Publisher · View at Google Scholar · View at Scopus
  60. K. Luu, C. J. Greenhill, A. Majoros, T. Decker, B. J. Jenkins, and A. Mansell, “STAT1 plays a role in TLR signal transduction and inflammatory responses,” Immunology and Cell Biology, vol. 92, no. 9, pp. 761–769, 2014. View at Publisher · View at Google Scholar · View at Scopus
  61. Y. Zhang, C. J. Ma, J. M. Wang et al., “Tim-3 regulates pro- and anti-inflammatory cytokine expression in human CD14+ monocytes,” Journal of Leukocyte Biology, vol. 91, no. 2, pp. 189–196, 2012. View at Publisher · View at Google Scholar · View at Scopus
  62. Y. Chen, M. Y. Hsieh, M. Y. Chang et al., “Eps8 protein facilitates phagocytosis by increasing TLR4-MyD88 protein interaction in lipopolysaccharide-stimulated macrophages,” Journal of Biological Chemistry, vol. 287, no. 22, pp. 18806–18819, 2012. View at Publisher · View at Google Scholar · View at Scopus
  63. P. Gong, D. J. Angelini, S. Yang et al., “TLR4 signaling is coupled to SRC family kinase activation, tyrosine phosphorylation of zonula adherens proteins, and opening of the paracellular pathway in human lung microvascular endothelia,” Journal of Biological Chemistry, vol. 283, no. 19, pp. 13437–13449, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. L. K. Ernst, A. M. Duchemin, and C. L. Anderson, “Association of the high-affinity receptor for IgG (Fc gamma RI) with the gamma subunit of the IgE receptor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 13, pp. 6023–6027, 1993. View at Publisher · View at Google Scholar
  65. D. Brooks, W. Qiu, A. Luster, and J. V. Ravetch, “Structure and expression of human IgG FcRII(CD32) functional heterogeneity is encoded by the alternatively spliced products of multiple genes,” The Journal of Experimental Medicine, vol. 170, no. 4, pp. 1369–1385, 1989. View at Publisher · View at Google Scholar
  66. I. E. Van den Herik-Oudijk, P. J. Capel, T. van der Bruggen, and J. G. Van de Winkel, “Identification of signaling motifs within human Fc gamma RIIa and Fc gamma RIIb isoforms,” Blood, vol. 85, no. 8, pp. 2202–2211, 1995. View at Google Scholar
  67. W. A. Jensen, S. Marschner, V. L. Ott, and J. C. Cambier, “FcγRIIB-mediated inhibition of T-cell receptor signal transduction involves the phosphorylation of SH2-containing inositol 5-phosphatase (SHIP), dephosphorylation of the linker of activated T-cells (LAT) and inhibition of calcium mobilization,” Biochemical Society Transactions, vol. 29, no. 6, pp. 840–846, 2001. View at Publisher · View at Google Scholar
  68. M. Ono, S. Bolland, P. Tempst, and J. V. Ravetch, “Role of the inositol phosphatase SHIP in negative regulation of the immune system by the receptor Fc(gamma)RIIB,” Nature, vol. 383, no. 6597, pp. 263–266, 1996. View at Publisher · View at Google Scholar · View at Scopus
  69. Y. Wang, Y. Wu, and Z. Wang, “Akt binds to and phosphorylates phospholipase C-γ1 in response to epidermal growth factor,” Molecular Biology of the Cell, vol. 17, no. 5, pp. 2267–2277, 2006. View at Publisher · View at Google Scholar · View at Scopus
  70. S. Bolland, R. N. Pearse, T. Kurosaki, and J. V. Ravetch, “SHIP modulates immune receptor responses by regulating membrane association of Btk,” Immunity, vol. 8, no. 4, pp. 509–516, 1998. View at Publisher · View at Google Scholar · View at Scopus
  71. S. Caserta, N. Nausch, A. Sawtell et al., “Chronic infection drives expression of the inhibitory receptor CD200R, and its ligand CD200, by mouse and human CD4 T cells,” PLoS One, vol. 7, no. 4, article e35466, 2012. View at Publisher · View at Google Scholar · View at Scopus
  72. G. J. Wright, M. J. Puklavec, A. C. Willis et al., “Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function,” Immunity, vol. 13, no. 2, pp. 233–242, 2000. View at Publisher · View at Google Scholar
  73. D. Hatherley, S. M. Lea, S. Johnson, and A. N. Barclay, “Structures of CD200/CD200 receptor family and implications for topology, regulation, and evolution,” Structure, vol. 21, no. 5, pp. 820–832, 2013. View at Publisher · View at Google Scholar · View at Scopus
  74. R. Mihrshahi, A. N. Barclay, and M. H. Brown, “Essential roles for Dok2 and RasGAP in CD200 receptor-mediated regulation of human myeloid cells,” The Journal of Immunology, vol. 183, no. 8, pp. 4879–4886, 2009. View at Publisher · View at Google Scholar · View at Scopus
  75. D. H. Josephs and D. Sarker, “Pharmacodynamic biomarker development for PI3K pathway therapeutics,” Translational Oncogenomics, vol. 7, pp. 33–49, 2016. View at Publisher · View at Google Scholar · View at Scopus
  76. M. Daëron, S. Jaeger, L. Du Pasquier, and E. Vivier, “Immunoreceptor tyrosine-based inhibition motifs: a quest in the past and future,” Immunological Reviews, vol. 224, no. 1, pp. 11–43, 2008. View at Publisher · View at Google Scholar · View at Scopus
  77. Z. Chen, P. A. Marsden, and R. M. Gorczynski, “Role of a distal enhancer in the transcriptional responsiveness of the human CD200 gene to interferon-γ and tumor necrosis factor-α,” Molecular Immunology, vol. 46, no. 10, pp. 1951–1963, 2009. View at Publisher · View at Google Scholar · View at Scopus
  78. D. A. Costello, A. Lyons, S. Denieffe, T. C. Browne, F. F. Cox, and M. A. Lynch, “Long term potentiation is impaired in membrane glycoprotein CD200-deficient mice: a role for toll-like receptor activation,” The Journal of Biological Chemistry, vol. 286, no. 40, pp. 34722–34732, 2011. View at Publisher · View at Google Scholar · View at Scopus
  79. M. D. Rosenblum, E. Olasz, J. E. Woodliff et al., “CD200 is a novel p53-target gene involved in apoptosis-associated immune tolerance,” Blood, vol. 103, no. 7, pp. 2691–2698, 2004. View at Publisher · View at Google Scholar · View at Scopus
  80. G. Dentesano, M. Straccia, A. Ejarque-Ortiz et al., “Inhibition of CD200R1 expression by C/EBP beta in reactive microglial cells,” Journal of Neuroinflammation, vol. 9, no. 1, p. 165, 2012. View at Publisher · View at Google Scholar · View at Scopus
  81. A. Lyons, K. McQuillan, B. F. Deighan et al., “Decreased neuronal CD200 expression in IL-4-deficient mice results in increased neuroinflammation in response to lipopolysaccharide,” Brain, Behavior, and Immunity, vol. 23, no. 7, pp. 1020–1027, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. A. Lyons, R. J. Griffin, C. E. Costelloe, R. M. Clarke, and M. A. Lynch, “IL-4 attenuates the neuroinflammation induced by amyloid-beta in vivo and in vitro,” Journal of Neurochemistry, vol. 101, no. 3, pp. 771–781, 2007. View at Publisher · View at Google Scholar · View at Scopus
  83. M. Deckert, J. D. Sedgwick, E. Fischer, and D. Schlüter, “Regulation of microglial cell responses in murine toxoplasma encephalitis by CD200/CD200 receptor interaction,” Acta Neuropathologica, vol. 111, no. 6, pp. 548–558, 2006. View at Publisher · View at Google Scholar · View at Scopus
  84. M. Cortez, C. Huynh, M. C. Fernandes, K. A. Kennedy, A. Aderem, and N. W. Andrews, “Leishmania promotes its own virulence by inducing expression of the host immune inhibitory ligand CD200,” Cell Host & Microbe, vol. 9, no. 6, pp. 463–471, 2011. View at Publisher · View at Google Scholar · View at Scopus
  85. S. Bhatnagar, K. Shinagawa, F. J. Castellino, and J. S. Schorey, “Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo,” Blood, vol. 110, no. 9, pp. 3234–3244, 2007. View at Publisher · View at Google Scholar · View at Scopus
  86. S. Mukhopadhyay, A. Plüddemann, J. Claire Hoe et al., “Immune inhibitory ligand CD200 induction by TLRs and NLRs limits macrophage activation to protect the host from meningococcal septicemia,” Cell Host & Microbe, vol. 8, no. 3, pp. 236–247, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. L. Peiser, K. Makepeace, A. Pluddemann et al., “Identification of neisseria meningitidis nonlipopolysaccharide ligands for class A macrophage scavenger receptor by using a novel assay,” Infection and Immunity, vol. 74, no. 9, pp. 5191–5199, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. R. D. Vicetti Miguel, S. A. K. Harvey, W. A. LaFramboise, S. D. Reighard, D. B. Matthews, and T. L. Cherpes, “Human female genital tract infection by the obligate intracellular bacterium chlamydia trachomatis elicits robust type 2 immunity,” PLoS One, vol. 8, no. 3, pp. e58565–e58511, 2013. View at Publisher · View at Google Scholar · View at Scopus
  89. G. Karnam, T. P. Rygiel, M. Raaben et al., “CD200 receptor controls sex-specific TLR7 responses to viral infection,” PLoS Pathogens, vol. 8, no. 5, pp. e1002710–e1002718, 2012. View at Publisher · View at Google Scholar · View at Scopus
  90. R. J. Snelgrove, J. Goulding, A. M. Didierlaurent et al., “A critical function for CD200 in lung immune homeostasis and the severity of influenza infection,” Nature Immunology, vol. 9, no. 9, pp. 1074–1083, 2008. View at Publisher · View at Google Scholar · View at Scopus
  91. J. Goulding, A. Godlee, S. Vekaria, M. Hilty, R. Snelgrove, and T. Hussell, “Lowering the threshold of lung innate immune cell activation alters susceptibility to secondary bacterial superinfection,” The Journal of Infectious Diseases, vol. 204, no. 7, pp. 1086–1094, 2011. View at Publisher · View at Google Scholar · View at Scopus
  92. R. J. Soberman, C. R. MacKay, C. A. Vaine et al., “CD200R1 supports HSV-1 viral replication and licenses pro-inflammatory signaling functions of TLR2,” PLoS One, vol. 7, no. 10, article e47740, 2012. View at Publisher · View at Google Scholar · View at Scopus
  93. M. Foster-Cuevas, T. Westerholt, M. Ahmed, M. H. Brown, A. N. Barclay, and S. Voigt, “Cytomegalovirus e127 protein interacts with the inhibitory CD200 receptor,” Journal of Virology, vol. 85, no. 12, pp. 6055–6059, 2011. View at Publisher · View at Google Scholar · View at Scopus
  94. C. L. Langlais, J. M. Jones, R. D. Estep, and S. W. Wong, “Rhesus rhadinovirus R15 encodes a functional homologue of human CD200,” Journal of Virology, vol. 80, no. 6, pp. 3098–3103, 2006. View at Publisher · View at Google Scholar · View at Scopus
  95. S. Zhang, H. Cherwinski, J. D. Sedgwick, and J. H. Phillips, “Molecular mechanisms of CD200 inhibition of mast cell activation,” The Journal of Immunology, vol. 173, no. 11, pp. 6786–6793, 2004. View at Publisher · View at Google Scholar