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Deprecated: Implicit conversion from float 284.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Immunology 2017 ; 150 (4): 495-505 Nephropedia Template TP
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NLRP3 inflammasome mediates interleukin?1? production in immune cells in response to Acinetobacter baumannii and contributes to pulmonary inflammation in mice #MMPMID28032341
Kang M; Jo S; Kim D; Park J
Immunology 2017[Apr]; 150 (4): 495-505 PMID28032341show ga
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?1? (IL?1?). 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?1? 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?1? production in macrophages in response to A. baumannii. Interleukin?1? 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?1? production and lung pathology.