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

Figure 2

Model for the activation of TLR4 in different settings of Leishmania infections. L. pifanoi amastigote-derived P8 glycolipid complex stimulates TLR4 in macrophages in an MD2, CD14, and MyD88-dependent manner, leading to the production of proinflammatory cytokines (left panel) [46]. Microenvironments during the activation of TLR4 in macrophages of C57BL6 mice by neutrophil elastase (NE): in (a), during the phagocytosis of L. major promastigotes, CR3, TLR4, and NE at the surface of macrophages increase parasite uptake but lead to ROS production and to partial parasite elimination within 24 h [47], the control of NE activity by parasite ISP2 prevents TLR4 activation and protects parasite from intracellular killing [47, 48]; in (b), macrophages remove apoptotic neutrophils by phagocytosis and acquire a M2b phenotype, leading to IL10 production and increased permissiveness to parasite growth; in (c), macrophages are infected by L. major and subsequently interact with apoptotic neutrophils, resulting in the activation of TLR4 by NE and in the production of TNF that promotes parasite killing.