| First Author | Zigdon M | Year | 2024 |
| Journal | PLoS Biol | Volume | 22 |
| Issue | 1 | Pages | e3002486 |
| PubMed ID | 38236896 | Mgi Jnum | J:346246 |
| Mgi Id | MGI:7580069 | Doi | 10.1371/journal.pbio.3002486 |
| Citation | Zigdon M, et al. (2024) Salmonella manipulates the host to drive pathogenicity via induction of interleukin 1beta. PLoS Biol 22(1):e3002486 |
| abstractText | Acute gastrointestinal infection with intracellular pathogens like Salmonella Typhimurium triggers the release of the proinflammatory cytokine interleukin 1beta (IL-1beta). However, the role of IL-1beta in intestinal defense against Salmonella remains unclear. Here, we show that IL-1beta production is detrimental during Salmonella infection. Mice lacking IL-1beta (IL-1beta -/-) 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 IL-1beta -/- mice which inhibited Salmonella expansion. Additionally, we found that IL-1beta induces expression of complement anaphylatoxins and suppresses the complement-inactivator carboxypeptidase N (CPN1). Disrupting this process via IL-1beta loss prevented mortality in Salmonella-infected IL-1beta -/- mice. Finally, we found that IL-1beta expression correlates with expression of the complement receptor in patients suffering from sepsis, but not uninfected patients and healthy individuals. Thus, Salmonella exploits IL-1beta signaling to outcompete commensal microbes and establish gut colonization. Moreover, our findings identify the intersection of IL-1beta signaling and the complement system as key host factors involved in controlling mortality during invasive Salmonellosis. |
