Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection.
Nat Immunol
; 14(5): 480-8, 2013 May.
Article
em En
| MEDLINE
| ID: mdl-23525089
ABSTRACT
NOD2 receptor and the cytosolic protein kinase RIPK2 regulate NF-κB and MAP kinase signaling during bacterial infections, but the role of this immune axis during viral infections has not been addressed. We demonstrate that Nod2(-/-) and Ripk2(-/-) mice are hypersusceptible to infection with influenza A virus. Ripk2(-/-) cells exhibited defective autophagy of mitochondria (mitophagy), leading to enhanced mitochondrial production of superoxide and accumulation of damaged mitochondria, which resulted in greater activation of the NLRP3 inflammasome and production of IL-18. RIPK2 regulated mitophagy in a kinase-dependent manner by phosphorylating the mitophagy inducer ULK1. Accordingly, Ulk1(-/-) cells exhibited enhanced mitochondrial production of superoxide and activation of caspase-1. These results demonstrate a role for NOD2-RIPK2 signaling in protection against virally triggered immunopathology by negatively regulating activation of the NLRP3 inflammasome and production of IL-18 via ULK1-dependent mitophagy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Infecções por Orthomyxoviridae
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Alphainfluenzavirus
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Proteína Serina-Treonina Quinase 2 de Interação com Receptor
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Inflamassomos
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Mitofagia
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Mitocôndrias
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article