Precarious balance: Th17 cells in host defense

Abstract

Lineage-specific responses from the effector T-cell repertoire form a critical component of adaptive immunity. The recent identification of Th17 cells-a third, distinct lineage of helper T cells-collapses the long-accepted paradigm in which Th1 and Th2 cells distinctly mediate cellular and humoral immunity, respectively. In this minireview, we discuss the involvement of the Th17 lineage during infection by extracellular bacteria, intracellular bacteria, and fungi. Emerging trends suggest that the Th17 population bridges innate and adaptive immunity to produce a robust antimicrobial inflammatory response. However, because Th17 cells mediate both host defense and pathological inflammation, elucidation of mechanisms that attenuate but do not completely abolish the Th17 response may have powerful implications for therapy.

FIG. 1.

Mucosal infection engages the Th17 axis of host defense. (A) Peripheral dendritic cells activated by pathogens produce IL-23, which upregulates IL-17 and IL-22 production from resident memory Th17 cells. (B) Synergy between IL-17 and IL-22 induces secretion of antimicrobial peptides from epithelial cells. (C) IL-17 also drives epithelial expression of granulopoeitic and chemotactic factors. (D) As innate immune cells accumulate at the mucosal surface, dendritic cells that have phagocytosed infected, apoptotic neutrophils respond by secreting proinflammatory cytokines that support Th17 differentiation from uncommitted infiltrating CD4⁺ T cells.