| Autor: |
Zigdon, Mor, Sawaed, Jasmin, Zelik, Lilach, Binyamin, Dana, Ben-Simon, Shira, Asulin, Nofar, Levin, Rachel, Modilevsky, Sonia, Naama, Maria, Telpaz, Shahar, Rubin, Elad, Awad, Aya, Sawaed, Wisal, Harshuk-Shabso, Sarina, Nuriel-Ohayon, Meital, Krishnamohan, Mathumathi, Werbner, Michal, Koren, Omry, Winter, Sebastian E., Apte, Ron N. |
| Předmět: |
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| Zdroj: |
PLoS Biology; 1/18/2024, Vol. 22 Issue 1, p1-21, 21p |
| Abstrakt: |
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. The gut microbiota protects the host by resisting the colonization of invasive food-borne pathogens, such as Salmonella. This study shows that Salmonella triggers the production of interleukin 1-beta, which induces the host to kill protective members of the microbiota thereby helping Salmonella to colonize the gut, and drives mortality during sepsis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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