A vital control of intracellular Chlamydia infection requires interleukin-17 receptor-mediated signaling (MUC3P.946)

Abstract

Abstract IL-17A is a pleiotropic proinflammatory cytokine that has a vital role in host resistance against extracellular bacterial and fungal infections. However, its role in controlling intracellular bacterial infection remains elusive. Here, we examined the IL-17/IL-17 receptor-mediated signaling in controlling intracellular Chlamydia muridarum infection in non-hematopoietic cells in vitro and in vivo. Remarkably, Chlamydia replication in mouse embryonic fibroblasts (MEF) was significantly increased in IL-17RC-knockout (IL-17RCKO) MEF and, to a lesser extent, in IL-17RAKO MEF compared to WT MEF at 6 and 12 hrs post-infection. To verify this finding in vivo, a respiratory Chlamydia infection model was established in bone marrow (BM) chimeric mice using WT BM donor cells transferred into γ-irradiated WT, IL-17RAKO and IL-17RCKO mice. Both IL-17RAKO and IL-17RCKO BM chimeric mice had significantly elevated bacterial burden in the lung compared to WT mice at days 5 and 11 post-infection. However, IL-17RCKO, but not IL-17RAKO, BM chimeric mice exhibited significant body weight loss compared to WT mice during early infection. While IL-17RAKO BM chimeric mice displayed an increased IL-17A response, IL-17RCKO mice showed an increased IFN-γ response in the lung. Our data demonstrates an indispensable role of the IL-17RC-mediated signaling in controlling Chlamydia infection and suggests differential roles of IL-17RA- and IL-17RC-mediated signaling in shaping Chlamydia-induced host responses.