The Intracellular Sensor NLRP3 Mediates Key Innate and Healing Responses to Influenza A Virus via the Regulation of Caspase-1

Paul G. Thomas, Pradyot Dash, Jerry R. Aldridge, Ali H. Ellebedy, Cory Reynolds, Amy J. Funk, William J. Martin, Mohamed Lamkanfi, Richard J. Webby, Kelli L. Boyd, Peter C. Doherty, Thirumala Devi Kanneganti

Research output: Contribution to journalArticlepeer-review

453 Scopus citations

Abstract

Virus-induced interlukin-1β (IL-1β) and IL-18 production in macrophages are mediated via caspase-1 pathway. Multiple microbial components, including viral RNA, are thought to trigger assembly of the cryopyrin inflammasome resulting in caspase-1 activation. Here, we demonstrated that Nlrp3-/- and Casp1-/- mice were more susceptible than wild-type mice after infection with a pathogenic influenza A virus. This enhanced morbidity correlated with decreased neutrophil and monocyte recruitment and reduced cytokine and chemokine production. Despite the effect on innate immunity, cryopyrin-deficiency was not associated with any obvious defect in virus control or on the later emergence of the adaptive response. Early epithelial necrosis was, however, more severe in the infected mutants, with extensive collagen deposition leading to later respiratory compromise. These findings reveal a function of the cryopyrin inflammasome in healing responses. Thus, cryopyrin and caspase-1 are central to both innate immunity and to moderating lung pathology in influenza pneumonia.

Original languageEnglish
Pages (from-to)566-575
Number of pages10
JournalImmunity
Volume30
Issue number4
DOIs
StatePublished - Apr 17 2009
Externally publishedYes

Keywords

  • MOLIMMUNO

Fingerprint Dive into the research topics of 'The Intracellular Sensor NLRP3 Mediates Key Innate and Healing Responses to Influenza A Virus via the Regulation of Caspase-1'. Together they form a unique fingerprint.

Cite this