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However, the role of IL-1\u03b2 in intestinal defense against\n                    <jats:italic>Salmonella<\/jats:italic>\n                    remains unclear. Here, we show that IL-1\u03b2 production is detrimental during\n                    <jats:italic>Salmonella<\/jats:italic>\n                    infection. Mice lacking IL-1\u03b2 (\n                    <jats:italic>IL-1\u03b2<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    ) failed to recruit neutrophils to the gut during infection, which reduced tissue damage and prevented depletion of short-chain fatty acid (SCFA)-producing commensals. Changes in epithelial cell metabolism that typically support pathogen expansion, such as switching energy production from fatty acid oxidation to fermentation, were absent in infected\n                    <jats:italic>IL-1\u03b2<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice which inhibited\n                    <jats:italic>Salmonella<\/jats:italic>\n                    expansion. Additionally, we found that IL-1\u03b2 induces expression of complement anaphylatoxins and suppresses the complement-inactivator carboxypeptidase N (CPN1). Disrupting this process via IL-1\u03b2 loss prevented mortality in\n                    <jats:italic>Salmonella<\/jats:italic>\n                    -infected\n                    <jats:italic>IL-1\u03b2<\/jats:italic>\n                    <jats:sup>-\/-<\/jats:sup>\n                    mice. Finally, we found that\n                    <jats:italic>IL-1\u03b2<\/jats:italic>\n                    expression correlates with expression of the complement receptor in patients suffering from sepsis, but not uninfected patients and healthy individuals. Thus,\n                    <jats:italic>Salmonella<\/jats:italic>\n                    exploits IL-1\u03b2 signaling to outcompete commensal microbes and establish gut colonization. Moreover, our findings identify the intersection of IL-1\u03b2 signaling and the complement system as key host factors involved in controlling mortality during invasive Salmonellosis.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3002486","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T13:40:48Z","timestamp":1705585248000},"page":"e3002486","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Salmonella manipulates the host to drive pathogenicity via induction of interleukin 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[cited 2023 May 23]. doi: 10.1126\/sciadv.abi9471","DOI":"10.1126\/sciadv.abi9471"},{"key":"pbio.3002486.ref031","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1046\/j.1365-2958.1998.00952.x","article-title":"A lethal role for lipid A in Salmonella infections","volume":"29","author":"SA Khan","year":"1998","journal-title":"Mol Microbiol"},{"key":"pbio.3002486.ref032","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/S1473-3099(21)00615-0","article-title":"Complications and mortality of non-typhoidal salmonella invasive disease: a global systematic review and meta-analysis","volume":"22","author":"CS Marchello","year":"2022","journal-title":"Lancet Infect Dis"},{"key":"pbio.3002486.ref033","unstructured":"Septicemia (Blood Poisoning): Causes, Management. In: Cleveland Clinic [Internet]. [cited 2023 May 23]. 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