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Francisella Tularensis: Activation of the Inflammasome
Author(s) -
WEISS DAVID S.,
HENRY THOMAS,
MONACK DENISE M.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1409.005
Subject(s) - francisella tularensis , francisella , inflammasome , tularemia , biology , innate immune system , pyroptosis , microbiology and biotechnology , caspase 1 , intracellular parasite , proinflammatory cytokine , aim2 , intracellular , immune system , immunology , inflammation , virulence , biochemistry , gene
Abstract: 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‐1β (IL‐1β) 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‐β 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.