title: Chlamydia pneumoniae harness host NLRP3 inflammasome-mediated caspase-1 activation for optimal intracellular growth in murine macrophages.
abstract: Chlamydia pneumoniae is an obligate intracellular pathogen that replicates within a vacuole and acquires host cell nutrients. We show that C. pneumoniae utilizes host innate immune signaling NLRP3/ASC/caspase-1 inflammasome for intracellular growth. Bone marrow-derived macrophages (BMMs) secreted mature interleukin-1β upon infection with C. pneumoniae depending on the NLRP3 inflammasome activation. Intracellular growth of C. pneumoniae was severely impaired in BMMs from Nlrp3(-/-), Asc(-/-), and Casp1(-/-) mice but not wild type or Nlrc4(-/-) mice. Furthermore defective NLRP3 inflammasome components led to accumulation of lipid droplets inside the infected BMMs, suggesting that uptake and/or utilization of lipids is disturbed in the absence of NLRP3 inflammasome activation. These results suggest C. pneumoniae has evolved to harness both host innate immune response and NLRP3 inflammasome activation, for the acquisition of essential nutrients necessary for intracellular growth. This unique property of C. pneumoniae may shed a new light on how C. pneumoniae increase the risk of atherosclerosis and metabolic syndrome.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan. Electronic address: ryito@fukuoka-u.ac.jp.
authors.forename: Ryota
authors.initials: R
authors.lastname: Itoh
authors.affiliation: Department of Microbiology and Immunology, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan; Department of Otolaryngology, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.
authors.forename: Issaku
authors.initials: I
authors.lastname: Murakami
authors.affiliation: Department of Microbiology and Immunology, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.
authors.forename: Bin
authors.initials: B
authors.lastname: Chou
authors.affiliation: Department of Microbiology and Immunology, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Department of Microbiology and Immunology, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Soejima
authors.affiliation: Department of Molecular Bacteriology and Immunology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0125, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Microbiology and Immunology, Faculty of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hiromatsu
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D001692:Biological Transport; D001854:Bone Marrow Cells / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics* / Q000276:immunology; D020170:Caspase 1 / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D016993:Chlamydophila pneumoniae / Q000502:physiology*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D007111:Immunity, Cellular; D007113:Immunity, Innate; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D066292:Lipid Droplets / Q000737:chemistry / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D061251:Primary Cell Culture; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; C512299:Ipaf protein, mouse; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C498534:Pycard protein, mouse; D020170:Caspase 1
keywords: Caspase-1; Chlamydia pneumoniae; Inflammasome; Lipid droplet