Microbial-induced Th17: superhero or supervillain?

Abstract

Th17 cells are an effector lineage of CD4 T cells that can contribute to protection against microbial pathogens and to the development of harmful autoimmune and inflammatory conditions. An increasing number of studies suggests that Th17 cells play an important protective role in mobilizing host immunity to extracellular and intracellular microbial pathogens, such as Candida and Salmonella. Furthermore, the generation of Th17 cells is heavily influenced by the normal microbial flora, highlighting the complex interplay among harmless microbes, pathogens, and host immunity in the regulation of pathogen-specific Th17 responses. In this article, we review the current understanding of microbe-induced Th17 cells in the context of infectious and inflammatory disease.

Figure 1. Induction of Th17-promoting cytokines by microbial products

C-type lectins Mincle, Dectin 1 and Dectin 2 as well as Mannose receptor are expressed on dendritic cells and macrophages and recognize fungal and mycobacterial components to activate Syk kinase and the CARD9 adaptor, leading to production of inflammatory cytokines that promote Th17 development in naïve T cells. Toll-like receptors (TLR) also recognize microbial products and induce production of both Th17 and Th1-promoting cytokines including IL-23 and IL-12. CLEC signaling modulates TLR signaling to downregulate Th1-promoting and favor Th17-promoting conditions, thus CLECs and TLRs co-operate to provide fine-tuning in the type of T helper response elicited.