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Cited by 438interferon and immune responsesImmune Response and InflammationCell death mechanisms and regulation

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

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Robinson, Nirmal, McComb, Scott, Mulligan, Rebecca, Dudani, Renu, Krishnan, Lakshmi, Sad, Subash·2012·Nature Immunology
DOI 10.1038/ni.2397PMC PMC4005791
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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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Cited by

Sorted by citations

Authors
Robinson, N., McComb, S., Mulligan, R., Dudani, R., Krishnan, L., & Sad, S.
Affiliations
  • Institute for Biological Sciences (CA)
  • University of Ottawa (CA)
Corresponding author
Sad, Subash
ORCID
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2012-08-26
Volume
13
Issue
10
Pages
954-962
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
DOI
10.1038/ni.2397
PMC
PMC4005791
OpenAlex
W1995878762
Cited by
438
References
7
Citations by year
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FWCI
16.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • NPARC (submittedVersion)
Funders
Canadian Institutes of Health Research (79412_1, 79412_2, 66538_1, 87055_1)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
type I interferon, necroptosis, macrophages, Salmonella typhimurium, RIP1 kinase, IFNAR1, host cell death, bacterial dissemination, host survival
MeSH terms
Animals, Interferon Type I, Macrophage Activation, Macrophages, Mice, Inbred C57BL, Salmonella Infections, Animal, Salmonella typhimurium, Signal Transduction, Apoptosis, GTPase-Activating Proteins, Mice, Receptor-Interacting Protein Serine-Threonine Kinases, Receptor, Interferon alpha-beta, Immune Evasion, Inflammasomes

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