Caspase-1 activity affects AIM2 speck formation/stability through a negative feedback loop.
Front Cell Infect Microbiol
; 3: 14, 2013.
Article
em En
| MEDLINE
| ID: mdl-23630667
ABSTRACT
The inflammasome is an innate immune signaling platform leading to caspase-1 activation, maturation of pro-inflammatory cytokines and cell death. Recognition of DNA within the host cytosol induces the formation of a large complex composed of the AIM2 receptor, the ASC adaptor and the caspase-1 effector. Francisella tularensis, the agent of tularemia, replicates within the host cytosol. The macrophage cytosolic surveillance system detects Francisella through the AIM2 inflammasome. Upon Francisella novicida infection, we observed a faster kinetics of AIM2 speck formation in ASC(KO) and Casp1(KO) as compared to WT macrophages. This observation was validated by a biochemical approach thus demonstrating for the first time the existence of a negative feedback loop controlled by ASC/caspase-1 that regulates AIM2 complex formation/stability. This regulatory mechanism acted before pyroptosis and required caspase-1 catalytic activity. Our data suggest that sublytic caspase-1 activity could delay the formation of stable AIM2 speck, an inflammasome complex associated with cell death.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Caspase 1
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Retroalimentação
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Francisella tularensis
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Macrófagos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Front Cell Infect Microbiol
Ano de publicação:
2013
Tipo de documento:
Article