Chlamydia trachomatisinfection renders M2 generation to mediated immunosuppression.

Abstract

Abstract Chlamydia trachomatis (C.tr) cause asymptomatic genital infections in women and is also a leading cause of preventable blindness. Limited mouse model of chronic C.tr infection are available to study the host immune response. We have developed BALB/c mice models of acute and chronic infections for C. trachomatisto explore the significance of macrophage-directed response in mediating immune activation/suppression. We observed that chronic and repeated infections accompanied abbrogated IFN-g and promoted enhanced TGF-β and IL-10 secretion. The signs of T cell exhaustion and anergy were also indicated during chronic and secondary infection. This skewed T cell response was established to be the regulated by alternatively-activated macrophages with low CD40 expression leading to sustained C. trachomatis genital infection. Macrophages under the influence of C. trachomatis infection or its secretome demonstrate an M2-macrophage subset phenotype which responded poorly to IFN-g owing to decreased IFNg-RI and IFNg-RII expression which correlated with decreased expression/release of MHC-II, CD40, iNOS and NO even following IFN-g treatment. Alternatively-activated M2 macrophages with low CD40 expression harbored high bacterial load and rendered the generation of immunosuppressive Th2 and Treg cells. Thus, C. trachomatis modulate the innate immune cells attenuating the anti-chlamydial functions of T cells in a manner that involves alleviated CD40 expression on macrophages.