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Alliance"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:p>\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    causes severe infections such as pneumonia and sepsis depending on the pore-forming toxin Panton\u2013Valentine 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\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    macrophages, or priming with LPS, restored C5aR1 expression and thereby PVL toxicity. In addition to promoting PVL-mediated killing, FBXO11 dampens secretion of IL-1\u03b2 after NLRP3 activation in response to bacterial toxins by reducing mRNA levels in a BCL-6\u2013dependent and BCL-6\u2013independent manner. Overall, these findings highlight that FBXO11 regulates C5aR1 and IL-1\u03b2 expression and controls macrophage cell death and inflammation following PVL exposure.\n                  <\/jats:p>","DOI":"10.26508\/lsa.202201735","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T15:30:15Z","timestamp":1680017415000},"page":"e202201735","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["FBXO11 governs macrophage cell death and inflammation in response to bacterial toxins"],"prefix":"10.26508","volume":"6","author":[{"given":"Yusun","family":"Jeon","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02bfwt286","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry & Molecular Biology, Monash Biomedicine Discovery Institute, Monash University","place":[", Clayton, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong 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