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NLRP3 inflammasome mediates interleukin-1 Beta production in immune cells in response to Acinetobacter baumannii and contributes to pulmonary inflammation in mice

Title
NLRP3 inflammasome mediates interleukin-1 Beta production in immune cells in response to Acinetobacter baumannii and contributes to pulmonary inflammation in mice
Authors
Kang, M.-J.[Kang, Min Jung]Jo, S.-G.[Jo, Sung Gang]Kim, D.-J.[Kim, Dong Jae]Park, J.-H.[Park, Jong Hwan]
DGIST Authors
Kim, D.-J.[Kim, Dong Jae]
Issue Date
2017
Citation
Immunology, 150(4), 495-505
Type
Article
Article Type
Article in Press
Keywords
Acinetobacter BaumanniiInterleukin-1 BetaMacrophagesNLRP3 Inflammasome
ISSN
0019-2805
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-1b 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. © 2016 John Wiley & Sons Ltd.
URI
http://hdl.handle.net/20.500.11750/2073
DOI
10.1111/imm.12704
Publisher
John Wiley and Sons
Files:
There are no files associated with this item.
Collection:
Laboratory Animal Resource Center1. Journal Articles


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