Type I interferon induces necroptosis in macrophages during infection with Salmonella enterica serovar Typhimurium
Date
2012
Authors
Robinson, N.
McComb, S.
Mulligan, R.
Dudani, R.
Krishnan, L.
Sad, S.
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Journal article
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Nature Immunology, 2012; 13(10):954-962
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Abstract
Salmonella 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.
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Data source: Supplementary information, https://doi.org/10.1038/ni.2397
Link to a related website: http://europepmc.org/articles/pmc4005791?pdf=render, Open Access via Unpaywall
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Copyright 2012 Nature America