The role of gap junction protein connexin 43 in Chlamydial pathogenesis (MUC7P.752)

Abstract

Abstract We have shown that Chlamydia-specific CD8 T cells do not significantly affect bacterial clearance but cause oviduct pathology, suggesting that they do not target infected cells efficaciously but cause pathology presumably by targeting uninfected cells. This suggests the possibility that chlamydial peptides are presented to CD8 T cells by uninfected cells, but begs the question: “How do uninfected cells acquire chlamydial peptides”? We hypothesized that gap junction mediated antigen transport (GMAT) via channels formed by connexin (Cx) proteins, predominantly Cx43 expressed on oviduct epithelium, contributes to this effect. We have found that HeLa cells engineered to express Cx43, but not those without, can efficaciously transfer Ova257-264 to co-cultured mouse APC, which subsequently activate CD8+ T cells from Ova primed OT-1 mice. Additionally, using Cre-Lox technology, we generated mice (Foxj1Cre-Cx43flox mice) with a conditional deficiency of Cx43 only in ciliated columnar epithelia, including oviducts. The Foxj1Cre-Cx43flox mice displayed comparable kinetics of vaginal chlamydial clearance, comparable splenic antigen-specific cytokine and serum antibody response, but significantly reduced oviduct pathology compared to WT mice on day 80 after intravaginal chlamydial infection. We have thus demonstrated the role of GMAT in immunopathogenesis of microbial infections.