Caspase-8 silences cell death-independent constitutive immune activation driven by tonic TNF-α

ABSTRACT: Caspase-8 is essential for maintaining organismal integrity by preventing cell death and subsequent inflammation in specific epithelial and endothelial tissues. Here we show that caspase-8 also controls a systemic, cell death-independent inflammatory pathway that is constitutively active during homeostasis. In vivo, selective caspase-8 inhibition produces, in the absence of other stimuli, marked neutrophilia driven by circulating proinflammatory and chemotactic cytokines and promotes bacterial clearance during infection. In vitro, caspase-8 inhibition triggers in neutrophils, but not in macrophages, a profound transcriptional response associated with the release of IL-1βand other cytokines. This process requires tonic TNF-α production by neutrophils, which acts autocrinally to sequentially

SUBMITTER: Giuseppe Teti 

PROVIDER: S-SCDT-10_1038-S44319-026-00813-5 | biostudies-other |

REPOSITORIES: biostudies-other