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Front Cell Infect Microbiol. 2013 Apr 24;3:14. doi: 10.3389/fcimb.2013.00014. eCollection 2013.

Caspase-1 activity affects AIM2 speck formation/stability through a negative feedback loop.

Author information

1
International Center for Infectiology Research, Université de Lyon Lyon, France.

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.

KEYWORDS:

AIM2; Francisella tularensis; caspase-1; inflammasome; regulation

PMID:
23630667
PMCID:
PMC3633939
DOI:
10.3389/fcimb.2013.00014
[Indexed for MEDLINE]
Free PMC Article

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