Caspase-8 promotes c-Rel-dependent inflammatory cytokine expression and resistance against Toxoplasma gondii

Caspase-8 is a critical regulator of apoptosis, programmed necrosis, and inflammatory gene expression. Caspase-8 is necessary for optimal transcription of inflammatory and antimicrobial host defense genes, including Il12 and Il1b. While the mechanisms of caspase-8-mediated control of apoptosis and programmed necrosis are well-described, how caspase-8 controls inflammatory gene expression is less clear. We show that caspase-8 is necessary for optimal nuclear translocation of the NF-κB family member c-Rel, and consequently, for recruitment of c-Rel to caspase-8-dependent gene promoters. Furthermore, caspase-8 deficiency led to an inability to control acute Toxoplasma gondii infection. These findings provide new insight into how caspase-8 contributes to inflammatory gene expression and host defense. Total RNA-sequencing