Abstract
Chlamydia trachomatis is an obligate intracellular bacterial pathogen that if left untreated can cause reproductive harm. Failure of natural adaptive immunity results in chronic and repeat infections. In efforts to understand the failure of adaptive immunity, we have previously discovered that CD8(+) T cells, normally integral for controlling intracellular pathogen infections, are misprogrammed by PD-1/PD-L1 signaling during in vivo C. trachomatis infection and fail to mount a protective response. Seeking to uncover the pathways and host factors involved in PD-L1 upregulation that may lead to CD8(+) T-cell inhibition, we discovered that C. trachomatis triggers the secretion of host type I interferons (IFNs) that are necessary and sufficient to upregulate PD-L1 in vitro. Additionally, secretion of type I IFNs is dependent on C. trachomatis development and its type III secretion system. We have also validated that type I IFNs contribute to upregulation of PD-L1 during C. trachomatis infection in vivo using a mouse model of infection. Overall, these findings reveal that C. trachomatis induction of this host pathway may contribute to adaptive immune evasion.