Influenza virus activates inflammasomes via its intracellular M2 ion channel.
Nat Immunol
; 11(5): 404-10, 2010 May.
Article
em En
| MEDLINE
| ID: mdl-20383149
ABSTRACT
Influenza virus, a negative-stranded RNA virus that causes severe illness in humans and animals, stimulates the inflammasome through the Nod-like receptor NLRP3. However, the mechanism by which influenza virus activates the NLRP3 inflammasome is unknown. Here we show that the influenza virus M2 protein, a proton-selective ion channel important in viral pathogenesis, stimulates the NLRP3 inflammasome pathway. M2 channel activity was required for the activation of inflammasomes by influenza and was sufficient to activate inflammasomes in primed macrophages and dendritic cells. M2-induced activation of inflammasomes required its localization to the Golgi apparatus and was dependent on the pH gradient. Our results show a mechanism by which influenza virus infection activates inflammasomes and identify the sensing of disturbances in intracellular ionic concentrations as a previously unknown pathogen-recognition pathway.
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Base de dados:
MEDLINE
Assunto principal:
Orthomyxoviridae
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Células Dendríticas
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Proteínas de Transporte
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Proteínas da Matriz Viral
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Infecções por Orthomyxoviridae
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Canais Iônicos
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Macrófagos
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article