Figure 6

Hypothetical model of responses of immune cells to SL. Classical activation of macrophages (M) and dendritic cells (DC) induces M1 and DC1 phenotypes, which drive CD4+ T cells toward Th1. In contrast, SL may selectively induce C-type lectin receptors and possibly other receptor classes on alternatively activated macrophages (M2), immature DC (DCi) and DC2 to preferentially induce Th2 cells [75]. Parasite antigens are presented to CD4+ T cells in lymphoid tissues. Upon activation, Th2 cells proliferate and induce immunoglobulin production, possibly down-regulating other Th subsets. However, different subsets can coexist and a balanced combination may result in susceptibility or resistance. Activated Th2 cells migrate to the site of SL attachment where they mediate expulsion of chalimus larvae. Antagonism within the Th compartment and suppression by Treg cells can inhibit CD4+ T cell effector functions. Several other mechanisms can have key functions in the shaping of the T cell repertoire, and in regulation of inflammatory responses to SL, including reciprocal Th17 and Treg differentiation mediated by vitamin A derivatives [107] and various anti-inflammatory agents, such as annexins. Programmed death ligand 1 (PD-L1) possibly provides a distinct negative regulatory checkpoint in T cell differentiation [98]. Endogenous products (e.g. cortisol and prostaglandins), cellular debris and SL products are also able to potently influence immune responses [108–110].