INVESTIGATING THE ROLE OF ACTIVATION-INDUCED CYTIDINE DEAMINASE IN CHLAMYDIA PATHOGENESIS

Abstract

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted infections around the world. The role of antibodies in Chlamydia pathogenesis remains inconclusive. Activation-induced cytidine deaminase (AID) is an enzyme critically required for B cell receptor diversification and the formation of high-affinity antibodies. The objective of this study is to determine the specific role of AID in murine models of primary and secondary Chlamydia genital infections using wild type (WT) and AID knockout (KO) mice. We showed that the bacterial burden, local immune cell infiltration and oviduct tissue pathology were comparable in two strains of mice following primary Chlamydia infection. In agreement with the known function of AID in secondary antibody production, AIDKO mice had minimal IgG1 and IgG2c production, but produced significantly greater IgM compared to WT mice. In addition, two strains of mice displayed divergent adaptive cellular immune profile following primary Chlamydia infection. While WT mice developed strong protective T helper 1 (Th1) immunity, AIDKO mice had elevated accumulation of suppressive regulatory T cells (Tregs) and follicular T helper cells (Tfh), the type of T cells collaborating with B cells for high-affinity antibody production. Accordingly, AIDKO mice had a delayed Chlamydia clearance, increased oviduct dilation and increased tissue inflammation compared to WT mice upon secondary challenge. Our data highlights a novel role of AID in host defense against Chlamydia infection via controlling both humoral and cellular immune responses. Further research is needed to dissect the mechanism whereby AID-deficiency in B cells affects the differentiation of T helper cells.