Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Francisella tularensis (F. tularensis) is a facultative intracellular pathogen that causes the systemic disease tularemia. This pathogen can replicate in the cytosol of macrophages, an ability that is linked with its virulence. We discuss recent data demonstrating that in macrophages, cytosolic Francisella induce the activation of the cysteine protease caspase-1 within a multiprotein complex called the inflammasome. NOD-like receptors (NLRs), which may have important roles in innate immunity as intracellular sensors of microbial components and cell injury, and the adaptor molecule ASC are thought to regulate caspase-1 within the inflammasome. Both ASC and caspase-1 play a critical role in host defense against Francisella infection in vivo. Activation of caspase-1 leads to the cleavage and activation of proinflammatory cytokines, such as interleukin-1beta (IL-1beta) and IL-18, as well as the induction of host cell death, which are required for innate immune defense against Francisella and other intracellular pathogens. The cytokine IFN-beta is secreted from infected cells in response to cytosolic Francisella and its signaling through the type I interferon receptor is required for activation of the inflammasome. Despite the effort of the host to induce inflammasome activation, Francisella modulates this host defense pathway, limiting its efficacy. These results highlight the role that the inflammasome plays in the tug-of-war between Francisella and the immune system.
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PMID:Francisella tularensis: activation of the inflammasome. 1739 24

A genomic locus called "region of difference 1" (RD1) in Mycobacterium tuberculosis has been shown to contribute to the generation of host protective immunity as well as to the virulence of the bacterium. To gain insight into the molecular mechanism, we investigated the difference in the cytokine-inducing ability between H37Rv and a mutant strain deficient for RD1 (DeltaRD1). We found that RD1 is implicated in the production of caspase-1-dependent cytokines, interleukin-18 (IL-18) and IL-1beta, from infected macrophages. The expression of these cytokines was similarly induced after infection with H37Rv and DeltaRD1. However, the activation of caspase-1 was observed only in H37Rv-infected macrophages. The cytokine production and caspase-1 activation were induced independently of type I interferon receptor signaling events. We also found that the activation of caspase-1 was markedly inhibited with increasing concentrations of extracellular KCl. Furthermore, the production of IL-18 and IL-1beta and caspase-1 activation were induced independently of a P2X7 purinergic receptor, and the inability of DeltaRD1 in caspase-1 activation was compensated for by nigericin, an agent inducing the potassium ion efflux. Based on these results, we concluded that RD1 participates in caspase-1-dependent cytokine production via induction of the potassium ion efflux in infected macrophages.
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PMID:The RD1 locus in the Mycobacterium tuberculosis genome contributes to activation of caspase-1 via induction of potassium ion efflux in infected macrophages. 1959 75