title: NLRP3 inflammasome mediates interleukin-1β production in immune cells in response to Acinetobacter baumannii and contributes to pulmonary inflammation in mice.
abstract: Acinetobacter baumannii is a multi-drug resistant, Gram-negative bacteria and infection with this organism is one of the major causes of mortality in intensive care units. Inflammasomes are multiprotein oligomers that include caspase-1, and their activation is required for maturation of interleukin-1β (IL-1β). Inflammasome signalling is involved in host defences against various microbial infections, but the precise mechanism by which A. baumannii activates inflammasomes and the roles of relevant signals in host defence against pulmonary A. baumannii infection are unknown. Our results showed that NLRP3, ASC and caspase-1, but not NLRC4, are required for A. baumannii-induced production of IL-1β in macrophages. An inhibitor assay revealed that various pathways, including P2X7R, K+efflux, reactive oxygen species production and release of cathepsins, are involved in IL-1β production in macrophages in response to A. baumannii. Interleukin-1β production in bronchoalveolar lavage (BAL) fluid was impaired in NLRP3-deficient and caspase-1/11-deficient mice infected with A. baumannii, compared with that in wild-type (WT) mice. However, the bacterial loads in BAL fluid and lungs were comparable between WT and NLRP3-deficient or caspase-1/11-deficient mice. The severity of lung pathology was reduced in NLRP3- deficient, caspase-1/11- deficient and IL-1-receptor-deficient mice, although the recruitment of immune cells and production of inflammatory cytokines and chemokines were not altered in these mice. These findings indicate that A. baumannii leads to the activation of NLRP3 inflammasome, which mediates IL-1β production and lung pathology.
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine and BK 21 PLUS Project Team, Chonnam National University, Gwangju, Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kang
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine and BK 21 PLUS Project Team, Chonnam National University, Gwangju, Korea.
authors.forename: Sung-Gang
authors.initials: SG
authors.lastname: Jo
authors.affiliation: Laboratory Animal Resource Centre, Daegu Gyeongbuk Institute of Science & Technology (DGIST), Daegu, Korea.
authors.forename: Dong-Jae
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine and BK 21 PLUS Project Team, Chonnam National University, Gwangju, Korea.
authors.forename: Jong-Hwan
authors.identifier: 0000-0003-4664-5640
authors.initials: JH
authors.lastname: Park
mesh_terms: D000151:Acinetobacter Infections / Q000276:immunology*; D040981:Acinetobacter baumannii / Q000276:immunology*; D000818:Animals; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D053471:Caspases, Initiator; D002478:Cells, Cultured; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism*; D011014:Pneumonia / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species; C101136:Casp4 protein, mouse; D020169:Caspases; D053471:Caspases, Initiator; D020170:Caspase 1
keywords: Acinetobacter baumannii; NLRP3 inflammasome; interleukin-1β; macrophages