Francisella tularensis: activation of the inflammasome.
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.
Weiss
David S
DS
Department of Microbiology and Immunology, Stanford University School of Medicine, 299 Campus Drive, Fairchild Building, Room D041, Stanford, CA 94305, USA.
Henry
Thomas
T
Monack
Denise M
DM
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D020170:Caspase 1 / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation; D005604:Francisella tularensis / Q000276:immunology* / Q000472:pathogenicity; D007113:Immunity, Innate / Q000502:physiology; D007370:Interferon Type I / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000201:enzymology / Q000276:immunology*; D046912:Multiprotein Complexes; D015398:Signal Transduction / Q000502:physiology; D014406:Tularemia
D000942:Antigens, Bacterial; D007370:Interferon Type I; D046912:Multiprotein Complexes; D020170:Caspase 1