Salmonellamanipulates the host to drive pathogenicity via induction of interleukin 1β

Author:

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,Werbner Michal,Koren Omry,Winter Sebastian E,Apte Ron N,Voronov Elena,Bel ShaiORCID

Abstract

AbstractAcute gastrointestinal infection with intracellular pathogens likeSalmonellaTyphimurium triggers the inflammasome and the release of the proinflammatory cytokine interleukin 1β (IL-1β). However, the role of IL-1β in intestinal defense againstSalmonellaremains unclear. Here, we show that IL-1β production is detrimental duringSalmonellainfection. 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-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 infectedIL-1β-/-mice which inhibitedSalmonellaexpansion. 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 completely prevented mortality inSalmonella-infectedIL-1β-/-mice and led to chronic infection. Thus,Salmonellaexploits 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.

Publisher

Cold Spring Harbor Laboratory

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