CARD9 facilitates microbe-elicited production of reactive oxygen species by regulating the LyGDI-Rac1 complex.
Nat Immunol
; 10(11): 1208-14, 2009 Nov.
Article
em En
| MEDLINE
| ID: mdl-19767757
ABSTRACT
In response to invading microorganisms, macrophages engage in phagocytosis and rapidly release reactive oxygen species (ROS), which serve an important microbicidal function. However, how phagocytosis induces ROS production remains largely unknown. CARD9, a caspase-recruitment domain (CARD)-containing protein, is important for resistance to fungal and bacterial infection. The mechanism of CARD9-mediated bacterial clearance is still mostly unknown. Here we show that CARD9 is required for killing intracellular bacteria in macrophages. CARD9 associated with the GDP-dissociation inhibitor LyGDI in phagosomes after bacterial and fungal infection and binding of CARD9 suppressed LyGDI-mediated inhibition of the GTPase Rac1, thereby leading to ROS production and bacterial killing in macrophages. Thus, our studies identify a key pathway that leads to microbe-elicited ROS production.
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Base de dados:
MEDLINE
Assunto principal:
Neuropeptídeos
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Fagossomos
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Proteínas
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Espécies Reativas de Oxigênio
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Proteínas rac de Ligação ao GTP
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Proteínas Adaptadoras de Transdução de Sinal
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Macrófagos
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article