Induction of Dendritic Cell Death by Chlamydia trachomatis

Abstract

The lack of effective adaptive immunity against Chlamydia trachomatis leads to chronic or repeated infection and serious disease sequelae. Dendritic cells (DCs) are professional antigen presenting cells crucial for the activation of T cells during C. trachomatis infection. cDC1s and cDC2s are the two main DC subsets responsible for T cell priming, but little is known about how C. trachomatis affects their ability to prime T cells. Using a mouse model of infection, we found that C. trachomatis uptake reduced the viability of cDC1s and cDC2s both in vitro and in vivo, with cDC1s experiencing more death. We validated our findings with human DCs in vitro, also observing C. trachomatis-induced cell death. Apoptosis was a major pathway of cell death, which was alleviated in Casp3/7 or Bak1/Bax knockout DCs. RNA sequencing of DCs from infected mice showed upregulation of genes involved in apoptosis upon infection, supporting our observations of DC death caused by C. trachomatis¬. In addition, we observed that C. trachomatis-specific CD8+ T cells were preferentially activated by cDC1s. Reduction in DC viability by C. trachomatis impaired the ability of infected DCs to activate T cells upon co-culture, although in the case of CD8+ T cell priming, controlling for viability was insufficient to fully rescue the defect. These results indicate that C. trachomatis may evade the adaptive immune system by directly inducing cell death in DCs.