Type I interferon induces necroptosis in macrophages during infection with Salmonella enterica serovar Typhimurium

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DOIResolve DOI: http://doi.org/10.1038/ni.2397
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TypeArticle
Journal titleNature Immunology
ISSN1529-2908
1529-2916
Volume13
Issue10
Pages954962; # of pages: 9
AbstractSalmonella enterica serovar Typhimurium (S. Typhimurium) is a virulent pathogen that induces rapid host death. Here we observed that host survival after infection with S. Typhimurium was enhanced in the absence of type I interferon signaling, with improved survival of mice deficient in the receptor for type I interferons (Ifnar1−/− mice) that was attributed to macrophages. Although there was no impairment in cytokine expression or inflammasome activation in Ifnar1−/− macrophages, they were highly resistant to S. Typhimurium–induced cell death. Specific inhibition of the kinase RIP1 or knockdown of the gene encoding the kinase RIP3 prevented the death of wild-type macrophages, which indicated that necroptosis was a mechanism of cell death. Finally, RIP3-deficient macrophages, which cannot undergo necroptosis, had similarly less death and enhanced control of S. Typhimurium in vivo. Thus, we propose that S. Typhimurium induces the production of type I interferon, which drives necroptosis of macrophages and allows them to evade the immune response.
Publication date
LanguageEnglish
AffiliationHuman Health Therapeutics; National Research Council Canada
Peer reviewedYes
NPARC number21268919
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Record identifier3ebd4629-ea09-40fe-a5ca-84c0f4061ba1
Record created2013-11-25
Record modified2016-05-09
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