Endogenous IL-17A mediated neutrophil infiltration by promoting chemokines expression during chlamydial lung infection.

Chlamydia is an obligate intracellular bacteria, which can infect cervix, urethra, conjunctiva, joints, lungs and so on. Neutrophils are important in host protection against microbial invasion during the early phase of infection. Here, to investigate the mechanism of IL-17A in recruiting neutrophils during Chlamydia muridarum (Cm) lung infection, we introduced IL-17A antibodies and IL-17-/- mice to confirm the effect of IL-17A on influencing neutrophil attractants expressions. From the analysis of the data, we found that showed that Cm infection could upregulate the expression of neutrophil-related chemokines such as KC, MIP-2 and IL-6, as well as adhesion molecules including ICAM-1 and VCAM-1. With blocking endogenous IL-17A, the upregulated MIP-2 and IL-6 were decreased, which induced less neutrophil recruitment in lung. Comparing to WT mice, IL-17-/- mice showed decreased infiltration of neutrophils in lung during the early phase of Cm infection, which were accordant with decreased chemokines, such as KC, MIP-2 and IL-6 expression. Whereas, the expression of adhesion molecules including ICAM and VCAM-1 in lungs were significantly increased in IL-17-/- mice comparing to WT mice during Cm lung infection. The results demonstrated that IL-17A influenced neutrophil infiltration by affecting expression of chemokines and adhesion molecules during the early phase of chlamydial lung infection.

Vγ4+ T Cells: A Novel IL-17-Producing γδ T Subsets during the Early Phase of Chlamydial Airway Infection in Mice.

Our previous studies showed that γδ T cells provided immune protection against Chlamydial muridarum (Cm), an obligate intracellular strain of chlamydia trachomatis, lung infection by producing abundant IL-17. In this study, we investigated the proliferation and activation of lung γδ T cell subsets, specifically the IL-17 and IFNγ production by them following Cm lung infection. Our results found that five γδ T cell subsets, Vγ1+ T, Vγ2+ T, Vγ4+ T, Vγ5+ T, and Vγ6+ T, expressed in lungs of naïve mice, while Cm lung infection mainly induced the proliferation and activation of Vγ4+ T cells at day 3 p.i., following Vγ1+ T cells at day 7 p.i. Cytokine detection showed that Cm lung infection induced IFNγ secretion firstly by Vγ4+ T cells at very early stage (day 3) and changed to Vγ1+ T cells at midstage (day 7). Furthermore, Vγ4+ T cell is the main γδ T cell subset that secretes IL-17 at the very early stage of Cm lung infection and Vγ1+ T cell did not secrete IL-17 during the infection. These findings provide in vivo evidence that Vγ4+T cells are the major IL-17 and IFNγ-producing γδ T cell subsets at the early period of Cm lung infection.