The role of immune cells in Chlamydiaspread to the gastrointestinal tract following reproductive tract infection

Abstract

Abstract Chlamydia trachomatisis the main cause of sexually transmitted disease and preventable blindness worldwide. In both animals and humans, Chlamydiaspp. infect not only the female reproductive tract (FRT), but also the gastrointestinal tract (GIT), where it persists for long periods, without causing obvious pathology. In the murine model, following FRT infection, Chlamydiaspreads to the GIT in stages and relies on carriage by host cells. After initial infection of epithelial cells in the FRT, lamina propria DCs internalize Chlamydia, which triggers their migration (and thus Chlamydiacarriage) to the FRT-draining iliac lymph nodes. In the ILNs, Chlamydiainfects other cells, which, then guided by the sphingosine 1-phosphate (S1P) gradient, enter the circulation, and carry Chlamydiato the spleen and the GIT. Selective depletion of either CD8 T cells, or monocytes/macrophages significantly lowers Chlamydiaburden in the spleen and the GIT. In contrast, depletion of CD4 T cells significantly increases Chlamydiaburden in the iliac lymph nodes and the GIT. While it takes about one week for FRT to GIT Chlamydiaspread, ceca of CD4 depleted mice become positive for Chlamydiaby day 3 of infection. It remains to be determined whether T cells and monocytes/macrophages become infected and actively transport Chlamydiato the GIT, or simply limit (or allow) its growth at different stages of infection and thus affect Chlamydiaspread. Delineating the interactions of Chlamydiawith specific host cells in vivoand identifying the cells and chemokines that mediate Chlamydiaspread will shed light on Chlamydiapathogenesis, and on regulation of host cell migration during Chlamydiainfection. Supported by grant from NIH (1 R21 AI159743-01)