Mitochondrial C5aR1 activity in macrophages controls IL-1β production underlying sterile inflammation.

ABSTRACT: While serum-circulating complement destroys invading pathogens, intracellularly active complement, termed the “complosome,” functions as a vital orchestrator of cell-metabolic events underlying T cell effector responses. Whether intracellular complement is also nonredundant for the activity of myeloid immune cells is currently unknown. Here, we show that monocytes and macrophages constitutively express complement component (C) 5 and generate autocrine C5a via formation of an intracellular C5 convertase. Cholesterol crystal sensing by macrophages induced C5aR1 signaling on mitochondrial membranes, which shifted ATP production via reverse electron chain flux toward reactive oxygen species generation and anaerobic glycolysis to favor IL-1β production, both at the transcriptional level and pro

SUBMITTER: Niyonzima N 

PROVIDER: S-EPMC8902698 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature