title: Francisella Inflammasomes: Integrated Responses to a Cytosolic Stealth Bacterium.
abstract: Francisella tularensis is a facultative intracellular bacterium causing tularemia, a zoonotic disease. Francisella replicates in the macrophage cytosol and eventually triggers cytosolic immune responses. In murine macrophages, Francisella novicida and Francisella tularensis live vaccine strain lyse in the host cytosol and activate the cytosolic DNA receptor Aim2. Here, we review the mechanisms leading or contributing to Aim2 inflammasome activation, including the role of TLRs and of IFN signaling and the implication of the guanylate-binding proteins 2 and 5 in triggering cytosolic bacteriolysis. Furthermore, we present how this cytosolic Gram-negative bacterium escapes recognition by caspase-11 but can trigger a non-canonical caspase-8 inflammasome. In addition, we highlight the differences in inflammasome activation in murine and human cells with pyrin, NLRP3, and AIM2 involved in sensing Francisella in human phagocytes. From a bacterial prospective, we describe the hiding strategy of Francisella to escape recognition by innate sensors and to resist to bacteriolysis in the host cytosol. Finally, we discuss the inability of the inflammasome sensors to detect F. tularensis subspecies tularensis strains, making them highly pathogenic stealth microbes.
authors.affiliation: Centre International de Recherche en Infectiologie, Lyon, France.|Inserm U1111, CNRS UMR5308, Lyon, France.|ENS Lyon, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Wallet
authors.affiliation: Centre International de Recherche en Infectiologie, Lyon, France.|Inserm U1111, CNRS UMR5308, Lyon, France.|ENS Lyon, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Lagrange
authors.affiliation: Centre International de Recherche en Infectiologie, Lyon, France. thomas.henry@inserm.fr.|Inserm U1111, CNRS UMR5308, Lyon, France. thomas.henry@inserm.fr.|ENS Lyon, Université Claude Bernard Lyon 1, Lyon, France. thomas.henry@inserm.fr.
authors.forename: Thomas
authors.initials: T
authors.lastname: Henry
mesh_terms: D000818:Animals; D003600:Cytosol / Q000276:immunology* / Q000382:microbiology; D005604:Francisella tularensis / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology*; D014406:Tularemia / Q000276:immunology* / Q000382:microbiology
chemical_list: D058847:Inflammasomes
keywords: AIM2; Cytosol; Francisella; Guanylate-binding proteins; Inflammasome; Tularemia