CD4+ T cell responses to the intracellular pathogen Chlamydia trachomatis

Abstract

Chlamydia trachomatis (C. trachomatis) is the most common cause of bacterial sexually transmitted infection (STI) in both men and women. Immunity to C. trachomatis involves many cell types, but CD4+ T cells play a crucial role in protecting the host during natural infection. Here we explored the mechanisms that lead to the successful development of CD4+ T cell responses and the mechanism by which these cells clear C. trachomatis infection. We find that type I interferon signaling contributes to the development of C. trachomatis- specific CD4+ T cell responses— demonstrating an important connection between innate signals and adaptive immunity. Previous studies show that IFNg production by CD4+ T cells is the main effector function responsible for bacterial clearance, yet the exact mechanism by which IFNg confers protection is poorly defined. This study shows that IFNg upregulates the expression of Major Histocompatibility Complex Class II (MHCII) on non-hematopoietic cells during C. trachomatis infection in vivo. Moreover, we find that MCHII expression on epithelial cells of the upper genital tract contributes to the efficient clearance of bacteria mediated by pathogen-specific CD4+ Th1 cells. As we further cataloged the protective mechanisms of C. trachomatis- specific CD4+ T cells, we show that T cells can express cytotoxic molecules such as granzyme B (GzmB) upon stimulation with C. trachomatis antigen both in vitro and in vivo. Importantly, we find that the development of cytotoxic effector functions by C. trachomatis- specific CD4+ T cells correlates to bacterial clearance. Taken together, our study suggests Chlamydia-specific CD4+ Th1 cells develop cytotoxic capacities that contribute to C. trachomatis.