The Role of IL-17A as a Potential Mediator of Chlamydial Pathogenesis
PURPOSE: IL-17 has been reported to play an important role in host defenses against pulmonary chlamydial infections by promoting a Th1 response. However, molecular mechanisms associated with IL-17 in genital chlamydial infection have not been well characterized and were the purpose of this study.
METHODS: C57BL/6 wild type (WT) and IL-17-/- mice were intravaginally challenged with C. muridarum (CM) and differences in infiltrating lymphocytes, T and B cell responses and miRNA expression were analyzed. We isolated RNA from the lower genital tracts of CM infected WT and IL-17A-/- mice and analyzed the gene transcripts with a high throughput qPCR based array for 84 genes associated with T and B cell activation.
RESULTS: Pathology was decreased at day 80 post challenge in IL-17A-/- compared to WT mice. Six genes were significantly (p<0.05) regulated at day 6 post-challenge including ICAM1 and IL-1β which are known mediators of pathology. These genes were further analyzed (miRNA based in silico prediction software); miRNA 214 was significantly upregulated in IL-17-/- mice, which has two target binding sites for the downregulated ICAM-1 gene. Additionally, we derived miR 214 over expressing genital cells which decreased ICAM-1 with CM infection in vitro. Furthermore, recruitment of neutrophils in IL-17 A-/- was reduced compared to WT mice.
CONCLUSION: Decreased pathology in IL-17 A-/- mice may be attributed to reduced expression of ICAM-1 leading to reduction in neutrophil infiltration at the early stage of genital infection.