FBXO11 governs macrophage cell death and inflammation in response to bacterial toxins.

ABSTRACT: Staphylococcus aureus causes severe infections such as pneumonia and sepsis depending on the pore-forming toxin Panton-Valentine leukocidin (PVL). PVL kills and induces inflammation in macrophages and other myeloid cells by interacting with the human cell surface receptor, complement 5a receptor 1 (C5aR1). C5aR1 expression is tighly regulated and may thus modulate PVL activity, although the mechanisms involved remain incompletely understood. Here, we used a genome-wide CRISPR/Cas9 screen and identified F-box protein 11 (FBXO11), an E3 ubiquitin ligase complex member, to promote PVL toxicity. Genetic deletion of FBXO11 reduced the expression of C5aR1 at the mRNA level, whereas ectopic expression of C5aR1 in FBXO11^-/- macrophages, or priming with LPS, restored C5aR1 express

SUBMITTER: Jeon Y 

PROVIDER: S-EPMC10053445 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature