Leptospira interrogans infection leads to IL-1β and IL-18 secretion from a human macrophage cell line through reactive oxygen species and cathepsin B mediated-NLRP3 inflammasome activation.

Autor: Li S; Guizhou Provincial Centre for Disease Control and Prevention, Guiyang, 550004, Guizhou, China; Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA, 94103, USA. Electronic address: zjumedjun@163.com., Wang M; Guizhou Provincial Centre for Disease Control and Prevention, Guiyang, 550004, Guizhou, China., Ojcius DM; Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA, 94103, USA., Zhou B; College of Animal Science, Guizhou University, Guiyang, 550025, Guizhou, China., Hu W; Department of Medical Microbiology and Parasitology, College of Medicine, Zhejiang University, Hangzhou, 310058, Zhejing, China., Liu Y; Guizhou Provincial Centre for Disease Control and Prevention, Guiyang, 550004, Guizhou, China., Ma Q; Guizhou Provincial Centre for Disease Control and Prevention, Guiyang, 550004, Guizhou, China., Tang G; Guizhou Provincial Centre for Disease Control and Prevention, Guiyang, 550004, Guizhou, China., Wang D; Guizhou Provincial Centre for Disease Control and Prevention, Guiyang, 550004, Guizhou, China., Yan J; Department of Medical Microbiology and Parasitology, College of Medicine, Zhejiang University, Hangzhou, 310058, Zhejing, China. Electronic address: med_bp@zju.edu.cn.
Jazyk: angličtina
Zdroj: Microbes and infection [Microbes Infect] 2018 Apr; Vol. 20 (4), pp. 254-260. Date of Electronic Publication: 2018 Feb 09.
DOI: 10.1016/j.micinf.2018.01.010
Abstrakt: Leptospirosis is a worldwide zoonosis caused by spirochetes from the genus Leptospira. Although there is a large diversity of clinical signs and symptoms, a severe inflammatory response is common to all leptospirosis patients. The mechanism of IL-1β secretion during Leptospira infection has been previously studied in mouse macrophages. However, the outcome of Leptospira infection is very different in human and murine macrophages, and the mechanisms responsible for IL-1β secretion in human macrophages had not been investigated. This study therefore examines the effects of Leptospira interrogans infection on inflammasome activation and proinflammatory cytokine expression in human macrophages. Increased mRNA and protein expression of NLRP3 was observed by real time RT-PCR and flow cytometry at 1 h after co-cultivation. Enzyme-linked immunosorbent assay (ELISA) determination showed that IL-1β and IL-18 are released in the culture supernatants at 1 h after cultivation. The inhibition assay showed that glybenclamide (a K + efflux inhibitor that blocks NLRP3 inflammasome activation) and N-benzyloxycarbony-Val-Ala-Asp (O-methyl)-fluoromethylketone (Z-VAD-FMK; a caspase-1 inhibitor) and NLRP3 depletion with siRNAs reduced the levels of IL-1β and IL-18 release. Moreover, the levels of IL-1β and IL-18 production decreased in CA-074 (a cathepsin B inhibitor) and NAC (an anti-oxidant) pretreated human macrophages, compared to untreated controls. This study suggests that L. interrogans infection leads to reactive oxygen species (ROS)- and cathepsin B-dependent NLRP3 inflammasome activation, which subsequently mediates caspase-1 activation and IL-1β and IL-18 release.
(Copyright © 2018 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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