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- Title
Caspase-1 activity affects AIM2 speck formation/stability through a negative feed back loop.
- Authors
Juruj, C.; Lelogeais, V.; Pierini, R.; Perret, M.; Py, B. F.; Jamilloux, Y.; Broz, P.; Ader, F.; Faure, M.; Henry, T.
- 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 ASCKO and Casp1KO 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.
- Subjects
CYTOKINES; CELL death; FRANCISELLA tularensis; FRANCISELLA; MACROPHAGES
- Publication
Frontiers in Cellular & Infection Microbiology, 2013, p1
- ISSN
2235-2988
- Publication type
Article
- DOI
10.3389/fcimb.2013.00014