The NLRP3 Inflammasome Mediates In Vivo Innate Immunity to Influenza A Virus through Recognition of Viral RNA
Open accessAbstract
The nucleotide-binding domain and leucine-rich-repeat-containing (NLR) family of pattern-recognition molecules mediate host immunity to various pathogenic stimuli. However, in vivo evidence for the involvement of NLR proteins in viral sensing has not been widely investigated and remains controversial. As a test of the physiologic role of the NLR molecule NLRP3 during RNA viral infection, we explored the in vivo role of NLRP3 inflammasome components during influenza virus infection. Mice lacking Nlrp3, Pycard, or caspase-1, but not Nlrc4, exhibited dramatically increased mortality and a reduced immune response after exposure to the influenza virus. Utilizing analogs of dsRNA (poly(I:C)) and ssRNA (ssRNA40), we demonstrated that an NLRP3-mediated response could be activated by RNA species. Mechanistically, NLRP3 inflammasome activation by the influenza virus was dependent on lysosomal maturation and reactive oxygen species (ROS). Inhibition of ROS induction eliminated IL-1beta production in animals during influenza infection. Together, these data place the NLRP3 inflammasome as an essential component in host defense against influenza infection through the sensing of viral RNA.
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NLRP3 seems to be important for the immune response to respiratory viruses.
“While NOD1 and NOD2, the first NLRs identified, are involved mainly in the recognition of bacterial peptidoglycans, NLRP3 seems to be important for the immune response to respiratory viruses (5, 118, 192, 280).”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [5]
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- Authors
- Allen, I. C., Scull, M. A., Moore, C. B., Holl, E. K., McElvania-TeKippe, E., Taxman, D. J., Guthrie, E. H., Pickles, R. J., & Ting, J. P.-Y.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Ting, Jenny P.-Y.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 30
- Issue
- 4
- Pages
- 556-565
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC2803103
- OpenAlex
- W1993728991
- Cited by
- 1,113
- References
- 35
- Citations by year
- 2026: 28 · 2025: 43 · 2024: 38 · 2023: 56 · 2022: 64 · 2021: 79 · 2020: 79 · 2019: 72 · 2018: 64 · 2017: 68 · 2016: 64 · 2015: 63 · 2014: 67 · 2013: 78 · 2012: 70
- FWCI
- 33.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Triangle Community Foundation
- National Institutes of Health
- U.S. Public Health Service (05-0064)
- National Institute of Allergy and Infectious Diseases (3-U54-AI057157-06S1, AI-067798, U19AI067798, 1U19-AI077437-01, U19AI077437, U54AI057157)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- NLRP3 inflammasome, influenza A virus, innate immunity, viral RNA sensing, pattern recognition receptors, caspase-1, IL-1β, reactive oxygen species, poly(I:C), PYCARD
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Carrier Proteins, Cell Line, Humans, Immunity, Innate, Influenza, Human, Orthomyxoviridae Infections, Influenza A virus, RNA, Viral, Virus Diseases, Mice, Knockout, Mice, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H3N2 Subtype, Exosomes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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