Salmonella manipulates the host to drive pathogenicity via induction of interleukin 1β.

Autor: Mor Zigdon, Jasmin Sawaed, Lilach Zelik, Dana Binyamin, Shira Ben-Simon, Nofar Asulin, Rachel Levin, Sonia Modilevsky, Maria Naama, Shahar Telpaz, Elad Rubin, Aya Awad, Wisal Sawaed, Sarina Harshuk-Shabso, Meital Nuriel-Ohayon, Mathumathi Krishnamohan, Michal Werbner, Omry Koren, Sebastian E Winter, Ron N Apte, Elena Voronov, Shai Bel
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: PLoS Biology, Vol 22, Iss 1, p e3002486 (2024)
Druh dokumentu: article
ISSN: 1544-9173
1545-7885
DOI: 10.1371/journal.pbio.3002486&type=printable
Popis: Acute gastrointestinal infection with intracellular pathogens like Salmonella Typhimurium triggers the release of the proinflammatory cytokine interleukin 1β (IL-1β). However, the role of IL-1β in intestinal defense against Salmonella remains unclear. Here, we show that IL-1β production is detrimental during Salmonella infection. Mice lacking IL-1β (IL-1β -/-) 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-1β -/- mice which inhibited Salmonella expansion. Additionally, we found that IL-1β induces expression of complement anaphylatoxins and suppresses the complement-inactivator carboxypeptidase N (CPN1). Disrupting this process via IL-1β loss prevented mortality in Salmonella-infected IL-1β -/- mice. Finally, we found that IL-1β expression correlates with expression of the complement receptor in patients suffering from sepsis, but not uninfected patients and healthy individuals. Thus, Salmonella exploits IL-1β signaling to outcompete commensal microbes and establish gut colonization. Moreover, our findings identify the intersection of IL-1β signaling and the complement system as key host factors involved in controlling mortality during invasive Salmonellosis.
Databáze: Directory of Open Access Journals
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