Article

The intracellular sensor NLRP3 mediates key innate and healing responses to influenza A virus via the regulation of caspase-1.

Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Immunity (impact factor: 21.64). 05/2009; 30(4):566-75. DOI:10.1016/j.immuni.2009.02.006 pp.566-75
Source: PubMed

ABSTRACT Virus-induced interlukin-1beta (IL-1beta) 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.

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Keywords

adaptive response
 
caspase-1 activation
 
caspase-1 pathway
 
chemokine production
 
cryopyrin-deficiency
 
cytokine
 
extensive collagen deposition
 
healing responses
 
IL-18 production
 
innate immunity
 
lung pathology
 
Multiple microbial components
 
pathogenic influenza
 
severe
 
virus control
 
Virus-induced interlukin-1beta
 
wild-type mice