Activation of NLRP3 by uropathogenic Escherichia coli is associated with IL-1? release and regulation of antimicrobial properties in human neutrophils.

ABSTRACT: The NLRP3 inflammasome and IL-1? have recently been linked to the severity of uropathogenic Escherichia coli (UPEC)-mediated urinary tract infection (UTI). However, not much is known about the contribution of NLRP3 to the antimicrobial properties of neutrophils and the release of IL-1? during UPEC infection. The purpose of this study was to elucidate the mechanisms behind UPEC-induced IL-1? release from human neutrophils, and to investigate the contribution of the NLRP3 inflammasome in neutrophil-mediated inhibition of UPEC growth. We found that the UPEC strain CFT073 increased the expression of NLRP3 and increased caspase-1 activation and IL-1? release from human neutrophils. The IL-1? release was mediated by the NLRP3 inflammasome and by serine proteases in an NF-?B-and cathepsin B-dependent manner. The UPEC virulence factors ?-hemolysin, type-1 fimbriae and p-fimbriae were all shown to contribute to UPEC mediated IL-1? release from neutrophils. Furthermore, inhibition of caspase-1 and NLRP3 activation increased neutrophil ROS-production, phagocytosis and the ability of neutrophils to suppress UPEC growth. In conclusion, this study demonstrates that UPEC can induce NLRP3 and serine protease-dependent release of IL-1? from human neutrophils and that NLRP3 and caspase-1 can regulate the antimicrobial activity of human neutrophils against UPEC.

SUBMITTER: Demirel I 

PROVIDER: S-EPMC7736892 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature