Chlamydia trachomatis impairs T cell priming by inducing dendritic cell death

TL;DR

Chlamydia trachomatis causes dendritic cell death, impairing T cell activation and weakening the immune response.

Contribution

This study reveals that C. trachomatis induces apoptosis in dendritic cells, impairing T cell priming and immune evasion.

Findings

C. trachomatis reduces viability of cDC1s and cDC2s, with cDC1s being more affected.

DC death is mainly apoptotic and reduced in Casp3/7 or Bak1/Bax knockout cells.

C. trachomatis-induced DC death impairs T cell activation, especially for CD8+ T cells.

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 that are 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. DC death was mainly due to apoptosis and is alleviated in Casp3/7 or Bak1/Bax knockout DCs. 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. RNA sequencing of DCs from infected mice showed upregulation of cell death pathways, supporting our observations of DC death caused by C. trachomatis. Finally, we validated our findings with human DCs in vitro, observing C. trachomatis-induced cell death. These results indicate that C. trachomatis may evade the adaptive immune system by directly inducing cell death in DCs.

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