Chlamydia trachomatis disturbs antigen cross-presentation by infected dendritic cells

Abstract

Chlamydia trachomatis (CT) is an obligate intracellular pathogen and the leading bacterial sexually transmitted infection worldwide. Inside the cell, CT lives into a parasitophorous vacuole (inclusion). Recently DC has begun to be studied like a CT host. Dendritic cells (DCs) can cross-present exogenous antigens to T CD8+ lymphocytes, a process that requires several intracellular transport pathways. Knowing that CT perturbs the intracellular transport, we hypothesized that chlamydia may alter antigen cross-presentation by disturbing key intracellular transport events. By using the DC line JAWS-II and the CT serovar L2, wee observed that CT evades most of the interaction with the endocytic pathway since CT does not localize to specific markers of early endosomes, lysosomes or multivesicular bodies. However, CT did showed a strong interaction with the recycling pathway marker TfR or with different Rab proteins that control endocytic recycling. . Also by confocal microscopy we evidenced a striking redistribution of MHC-I molecules in CT infected DCs. These cells lost their typical MHC-I location in both, the perinuclear recycling center and the plasma membrane. By flow cytometry and WB analysis, we confirmed that MHC-I molecules do not transport properly to the cell surface in infected DCs, as compared to uninfected cells. Although the total amounts of MHC-I molecules are similar in both conditions. . By using the model antigen ovalbumin (OVA) and the specific CD8+ T lymphocytes (B3Z) to measure cross-presentation, we found a significant decrease in the cross-presentation ability of infected DCs with both, soluble and latex beads-associated OVA. Finally, we discarded that this effect is caused by loss of endocytic capacity in the infected DC, since the endocytosis rate remained unchanged after chlamydia infection. Altogether these results indicate that CT infection alters the normal MHC-I intracellular distribution and impairs antigen cross-presentation by DCs.