Figure 3.

Integration of CLR -mediated signaling directs adaptive immunity. CLR-mediated recognition of fungi drives their uptake and killing by phagocytes, and directs the development of protective Th1/Th17 responses. Induction of IL-12 drives IFN-γ production by Th1 and iNKT cells, which is critically required for the activation of phagocytes. Remarkably, production of IFN-γ by self-reactive iNKT cells occurs following CLR-mediated induction of IL-12 on antigen-presenting cells. On the other hand, induction of IL-1β, IL-6, and IL-23 promotes Th17 differentiation, which drives the production of IL-17 and IL-22. These cytokines are critically required for neutrophil recruitment and epithelial antimicrobial peptide (AMP) production and provide protection against fungal infections, particularly at the mucosa. Notably, the production of IL-17 can also be directly induced by CLRs expressed on γδ T cells, without TCR triggering.