NLRP3 (NALP3/CIAS1/Cryopyrin) mediates key innate and healing responses to influenza A virus via the regulation of caspase-1

By P. Thomas, P. Dash, Jerry R. Aldridge, A. Ellebedy, Cory E. Reynolds, A. Funk, W. Martin, M. Lamkanfi, R. Webby, K. Boyd and 2 more. Immunity, 2009

745 citations recorded by the source corpus.

SUMMARY Virus-induced IL-1β and IL-18 production in macrophages is mediated via a caspase-1 pathway. Multiple microbial components, including viral RNA, are thought to trigger assembly of the cryopyrin inflammasome and consequent caspase-1 activation. Here we demonstrate that cryopyrin−/− and caspase-1−/− mice are more susceptible than wildtype controls following infection with a pathogenic influenza A virus. This profile of enhanced morbidity correlates 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 novel function of the cryopyrin inflammasome in healing responses. Cryopyrin and caspase-1 are clearly central to both innate immunity and to moderating lung pathology in influenza pneumonia.

Subfields: Epidemiology, Immunology

View Paper: https://www.semanticscholar.org/paper/594ccc37fdfcc681c6580d7f9c1c9f8a23a50ccb

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. M. Lamkanfi
2. A. Iwasaki
3. V. Dixit
4. Haitao Wen
5. T. Kanneganti
6. J. Ting

In Immunology

1. T. Kanneganti
2. R. Malireddi
3. S. Kesavardhana
4. M. Lamkanfi
5. V. Dixit
6. A. Iwasaki
7. J. Ting
8. S. Man

Citations in the corpus

• ZBP1/DAI is an innate sensor of influenza virus triggering the NLRP3 inflammasome and programmed cell death pathways (2016, positive): “Unlike the detrimental effects of apoptosis and necroptosis, NLRP3 inflammasome activation leading to pyroptosis and release of proinflammatory cytokines IL-1β and IL-18 is protective during acute IAV infection (8, 9).”
• Redox Regulation of NLRP3 Inflammasomes: ROS as Trigger or Effector? (2015, neutral): “coli, Neisseria gonorrhoe, and Candida albicans (36,55,59,76,95,125).”
• Microbiota regulates immune defense against respiratory tract influenza A virus infection (2011, background): “Two other groups, using high lethal doses of influenza virus challenge, demonstrated that in the absence of the NLRP3 inflammasome, mice succumb to high doses of A/PR8 infection due to innate immune defects (4, 5).”
• Inflammasomes and their roles in health and disease. (2012, background): “F or p er so na l u se o nl y. gene duplication events that occurred after the bifurcation of rodents and primates gave rise to 34 NLR genes in the mouse genome (Tian et al. 2009).”
• ZBP1 and TAK1: Master Regulators of NLRP3 Inflammasome/Pyroptosis, Apoptosis, and Necroptosis (PAN-optosis) (2019, background): “Furthermore, IAV-induced activation of the NLRP3 inflammasome controls viral spread and protects against lung damage, promoting host-protective immune responses (Allen et al., 2009; Thomas et al., 2009).”
• The Inflammasome NLRs in Immunity, Inflammation, and Associated Diseases (2011, background): “mortality and morbidity during influenza infection that is associated with increased necrosis and collagen deposition (63).”