Toll-Like Receptors in Leishmania Infections: Guardians or Promoters?

Figure 3

Proposed models for the activation of intracellular TLR9 and TLR3 by Leishmania. TLR9 of plasmocytoid DCs (pDCs) can be activated by putative TLR9 ligands secreted by L. infantum promastigotes and taken up by endocytosis or in endosomal compartments. TLR9 in myeloid DCs (mDCs) can be activated by L. infantum DNA after parasite phagocytosis and destruction in the endosomal compartment, leading to the activation of NK cells and protective Th1 responses [4, 63, 64]. TLR3 is required for the production of TNF, NO and the phagocytosis of L. donovani by macrophages, suggesting a protective role for infection [67]. Intracellular TLR3 is activated in a TRIF-dependent pathway in macrophages infected with metastatic L. guyanensis, by double-stranded RNA from the Leishmania virus LRV1 [68]. This leads to the production of proinflammatory cytokines and chemokines, as well as type1-IFNs. Despite the inflammatory response, TLR3 is required for the effective development of footpad swelling, for significant parasite burden and its dissemination in infected hamsters, suggesting that TLR3 activation facilitates disease pathology by parasites of the Leishmania Viannia subgenus.