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

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. ApteElena Voronov, Shai Bel

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere3002486
JournalPLoS Biology
Volume22
Issue number1
DOIs
StatePublished - Jan 2024

Bibliographical note

Publisher Copyright:
© 2024 Zigdon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding

This work was supported by the Azrieli Foundation Early Career Faculty Fellowship (to SB), the Israeli Science Foundation (ISF) (925/19 and 1851/19 to SB), the European Research Council (ERC) Starting Grant (GCMech 101039927 to SB) and the U.S-Israel Binational Science Foundation (2021025 to SEW and SB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

FundersFunder number
European CommissionGCMech 101039927
United States-Israel Binational Science Foundation2021025
Israel Science Foundation1851/19, 925/19
Azrieli Foundation

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