title: Inflammasome Recognition and Regulation of the Legionella Flagellum.
abstract: The Gram-negative bacterium Legionella pneumophila colonizes extracellular environmental niches and infects free-living protozoa. Upon inhalation into the human lung, the opportunistic pathogen grows in macrophages and causes a fulminant pneumonia termed Legionnaires' disease. L. pneumophila employs a biphasic life cycle, comprising a replicative, non-virulent, and a stationary, virulent form. In the latter phase, the pathogen produces a plethora of so-called effector proteins, which are injected into host cells, where they subvert pivotal processes and promote the formation of a distinct membrane-bound compartment, the Legionella-containing vacuole. In the stationary phase, the bacteria also produce a single monopolar flagellum and become motile. L. pneumophila flagellin is recognized by and triggers the host's NAIP5 (Birc1e)/NLRC4 (Ipaf) inflammasome, which leads to caspase-1 activation, pore formation, and pyroptosis. The production of L. pneumophila flagellin and pathogen-host interactions are controlled by a complex stationary phase regulatory network, detecting nutrient availability as well as the Legionella quorum sensing (Lqs) signaling compound LAI-1 (3-hydroxypentadecane-4-one). Thus, the small molecule LAI-1 coordinates L. pneumophila flagellin production and motility, inflammasome activation, and virulence.
authors.affiliation: Max von Pettenkofer Institute, Ludwig-Maximilians University, Pettenkoferstraße 9a, 80336, Munich, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Schell
authors.affiliation: Institute of Medical Microbiology, University of Zürich, Gloriastrasse 30/32, 8006, Zürich, Switzerland.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Simon
authors.affiliation: Institute of Medical Microbiology, University of Zürich, Gloriastrasse 30/32, 8006, Zürich, Switzerland. hilbi@imm.uzh.ch.
authors.forename: Hubert
authors.initials: H
authors.lastname: Hilbi
mesh_terms: D000818:Animals; D005407:Flagella / Q000235:genetics / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D058847:Inflammasomes / Q000235:genetics / Q000276:immunology*; D016952:Legionella pneumophila / Q000235:genetics / Q000276:immunology*; D007877:Legionnaires' Disease / Q000235:genetics / Q000276:immunology* / Q000382:microbiology
chemical_list: D058847:Inflammasomes
keywords: Amoeba; Autoinducer; Dictyostelium; Effector protein; Flagellin; Macrophage; NAIP5/NLRC4 inflammasome; Pathogen vacuole; Phosphoinositide; Quorum sensing; Small GTPase; Type IV secretion