title: Capsular Polysaccharide Is Involved in NLRP3 Inflammasome Activation by Klebsiella pneumoniae Serotype K1.
abstract: Klebsiella pneumoniae (strain 43816, K2 serotype) induces interleukin-1β (IL-1β) secretion, but neither the bacterial factor triggering the activation of these inflammasome-dependent responses nor whether they are mediated by NLRP3 or NLRC4 is known. In this study, we identified a capsular polysaccharide (K1-CPS) in K. pneumoniae (NTUH-K2044, K1 serotype), isolated from a primary pyogenic liver abscess (PLA K. pneumoniae), as the Klebsiella factor that induces IL-1β secretion in an NLRP3-, ASC-, and caspase-1-dependent manner in macrophages. K1-CPS induced NLRP3 inflammasome activation through reactive oxygen species (ROS) generation, mitogen-activated protein kinase phosphorylation, and NF-κB activation. Inhibition of both the mitochondrial membrane permeability transition and mitochondrial ROS generation inhibited K1-CPS-mediated NLRP3 inflammasome activation. Furthermore, IL-1β secretion in macrophages infected with PLA K. pneumoniae was shown to depend on NLRP3 but also on NLRC4 and TLR4. In macrophages infected with a K1-CPS deficiency mutant, an lipopolysaccharide (LPS) deficiency mutant, or K1-CPS and LPS double mutants, IL-1β secretion levels were lower than those in cells infected with wild-type PLA K. pneumoniae. Our findings indicate that K1-CPS is one of the Klebsiella factors of PLA K. pneumoniae that induce IL-1β secretion through the NLRP3 inflammasome.
authors.affiliation: Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan kuofenghua@gmail.com shwu@gate.sinica.edu.tw.
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Hua
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
authors.forename: Feng-Ling
authors.initials: FL
authors.lastname: Yang
authors.affiliation: Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan.
authors.forename: Hsiao-Wen
authors.initials: HW
authors.lastname: Chiu
authors.affiliation: Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan.
authors.forename: Ju-Ching
authors.initials: JC
authors.lastname: Chou
authors.affiliation: Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan.
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Dong
authors.affiliation: Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan.
authors.forename: Chien-Nan
authors.initials: CN
authors.lastname: Lin
authors.affiliation: Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan.
authors.forename: Chai-Yi
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Microbiology, National Taiwan University, Taipei, Taiwan Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jin-Town
authors.initials: JT
authors.lastname: Wang
authors.affiliation: Department of Laboratory, Kunming Branch, Taipei City Hospital, Taipei, Taiwan.
authors.forename: Lan-Hui
authors.initials: LH
authors.lastname: Li
authors.affiliation: Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan.
authors.forename: Huan-Wen
authors.initials: HW
authors.lastname: Chiu
authors.affiliation: Department of Biomechatronic Engineering, National Ilan University, Ilan, Taiwan.
authors.forename: Yi-Chich
authors.initials: YC
authors.lastname: Chiu
authors.affiliation: Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan kuofenghua@gmail.com shwu@gate.sinica.edu.tw.
authors.forename: Shih-Hsiung
authors.initials: SH
authors.lastname: Wu
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000276:immunology*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D058847:Inflammasomes / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology; D007710:Klebsiella Infections / Q000276:immunology*; D007711:Klebsiella pneumoniae / Q000276:immunology*; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000942:Antigens, Bacterial; D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C492716:Nlrp3 protein, mouse; D011135:Polysaccharides, Bacterial; C036962:capsular polysaccharide K1