Type I IFNs contribute to upregulation of PD-L1 duringinfection.

Abstract

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 CD8T cells, normally integral for controlling intracellular pathogen infections, are misprogrammed by PD-1/PD-L1 signaling duringinfection and fail to mount a protective response. Seeking to uncover the pathways and host factors involved in PD-L1 upregulation that may lead to CD8T-cell inhibition, we discovered thattriggers the secretion of host type I interferons (IFNs) that are necessary and sufficient to upregulate PD-L1. Additionally, secretion of type I IFNs is dependent ondevelopment and its type III secretion system. We have also validated that type I IFNs contribute to upregulation of PD-L1 duringinfectionusing a mouse model of infection. Overall, these findings reveal thatinduction of this host pathway may contribute to adaptive immune evasion.