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The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA.

Publication ,  Journal Article
Allen, IC; Scull, MA; Moore, CB; Holl, EK; McElvania-TeKippe, E; Taxman, DJ; Guthrie, EH; Pickles, RJ; Ting, JP-Y
Published in: Immunity
April 17, 2009

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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Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

April 17, 2009

Volume

30

Issue

4

Start / End Page

556 / 565

Location

United States

Related Subject Headings

  • Virus Diseases
  • RNA, Viral
  • Orthomyxoviridae Infections
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Mice, Knockout
  • Mice
  • Influenza, Human
  • Influenza A virus
  • Influenza A Virus, H3N2 Subtype
  • Influenza A Virus, H1N1 Subtype
 

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Allen, I. C., Scull, M. A., Moore, C. B., Holl, E. K., McElvania-TeKippe, E., Taxman, D. J., … Ting, J.-Y. (2009). The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity, 30(4), 556–565. https://doi.org/10.1016/j.immuni.2009.02.005
Allen, Irving C., Margaret A. Scull, Chris B. Moore, Eda K. Holl, Erin McElvania-TeKippe, Debra J. Taxman, Elizabeth H. Guthrie, Raymond J. Pickles, and Jenny P-Y Ting. “The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA.Immunity 30, no. 4 (April 17, 2009): 556–65. https://doi.org/10.1016/j.immuni.2009.02.005.
Allen IC, Scull MA, Moore CB, Holl EK, McElvania-TeKippe E, Taxman DJ, et al. The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity. 2009 Apr 17;30(4):556–65.
Allen, Irving C., et al. “The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA.Immunity, vol. 30, no. 4, Apr. 2009, pp. 556–65. Pubmed, doi:10.1016/j.immuni.2009.02.005.
Allen IC, Scull MA, Moore CB, Holl EK, McElvania-TeKippe E, Taxman DJ, Guthrie EH, Pickles RJ, Ting JP-Y. The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity. 2009 Apr 17;30(4):556–565.
Journal cover image

Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

April 17, 2009

Volume

30

Issue

4

Start / End Page

556 / 565

Location

United States

Related Subject Headings

  • Virus Diseases
  • RNA, Viral
  • Orthomyxoviridae Infections
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Mice, Knockout
  • Mice
  • Influenza, Human
  • Influenza A virus
  • Influenza A Virus, H3N2 Subtype
  • Influenza A Virus, H1N1 Subtype