Respective IL-17A production by γδ T and Th17 cells and its implication in host defense against chlamydial lung infection.

Abstract

The role of IL-17A is important in protection against lung infection with Chlamydiae, an obligate intracellular bacterial pathogen. In this study, we explored the producers of IL-17A in chlamydial lung infection and specifically tested the role of major IL-17A producers in protective immunity. We found that γδT cells and Th17 cells are the major producers of IL-17A at the early and later stages of chlamydial infection, respectively. Depletion of γδT cells in vivo at the early postinfection (p.i.) stage, when most γδT cells produce IL-17A, failed to alter Th1 responses and bacterial clearance. In contrast, the blockade of IL-17A at the time when IL-17A was mainly produced by Th17 (day 7 p.i.) markedly reduced the Th1 response and increased chlamydial growth. The data suggest that the γδ T cell is the highest producer of IL-17A in the very early stages of infection, but the protection conferred by IL-17A is mainly mediated by Th17 cells. In addition, we found that depletion of γδ T cells reduced IL-1α production by dendritic cells, which was associated with a reduced Th17 response. This finding is helpful to understand the variable role of IL-17A in different infections and to develop preventive and therapeutic approaches against infectious diseases by targeting IL-17A.