Mechanisms of antigen transport from the female reproductive tract to the gastrointestinal tract

Abstract

One of the major functions of the female reproductive tract (FRT) is the establishment and maintenance of pregnancy, resulting in healthy offspring. Although many pathogens (e.g. Chlamydia spp.) infect the FRT, no vaccines against these pathogens have been licensed to date. This lack of success has been in part attributed to the inability of the FRT to efficiently internalize antigens. We showed that FRT epithelium of mice can internalize nanoparticles (NPs) < 40 nm and that protein coated 20 nm NPs prime the intestinal mucosa for secretion of IgA. This finding led us to hypothesize that NPs reach the GI tract following per-vaginal (PV) instillation. Using multiphoton and fluorescence microscopy, we show that PV-instilled antigens (DAPI, Dextran, NPs) reach the stomach antrum and the small intestine within 1–3 h. It is proposed that Chlamydia spp. colonizes the GI tract following PV instillation by entering the circulation. We show that colonization of the GI tract by C. muridarum is dependent on cell transport. While within 7 days of PV infection Chlamydia colonizes the GI tract of controls, while no Chlamydia can be detected in iliac lymph nodes (ILNs) or GI tracts of CCR7−/− mice. Moreover, treatment of mice with FTY720 inhibits colonization of the GI tract, but it does not preclude infection of ILNs by Chlamydia. This finding indicates that Chlamydia transport from the ILNs to the GI tract depends on sphingosine 1-phosphate-mediated cell egress. Elucidation of mechanisms by which C. muridarum disseminates systemically to colonize the lymphoid tissues and the GI tract will be important for understanding both the immunity to and pathogenesis of Chlamydia spp.