Culling of APCs by inflammatory cell death pathways restricts TIM3 and PD-1 expression and promotes the survival of primed CD8 T cells.

ABSTRACT: We evaluated the impact of premature cell death of antigen-presenting cells (APCs) by Caspase-1- and RipK3-signaling pathways on CD8⁺ T-cell priming during infection of mice with Salmonella typhimurium (ST). Our results indicate that Caspase1 and RipK3 synergize to rapidly eliminate infected APCs, which does not influence the initial activation of CD8⁺ T cells. However, the maintenance of primed CD8⁺ T cells was greatly compromised when both these pathways were disabled. Caspase-1- and RipK3-signaling did not influence NF-κB signaling in APCs, but synergized to promote processing of IL-1 and IL-18. Combined deficiency of Caspase1 and RipK3 resulted in compromised innate immunity and accelerated host fatality due to poor processing of IL-18. In contrast, syn

SUBMITTER: Patel R 

PROVIDER: S-EPMC5635216 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature