Mycobacterial infection induces higher interleukin-1β and dysregulated lung inflammation in mice with defective leukocyte NADPH oxidase

Wen Cheng Chao, Chia Liang Yen, Cheng Yuan Hsieh, Ya Fang Huang, Yau Lin Tseng, Peter Andrija Nigrovic, Chi Chang Shieh

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Granulomatous inflammation causes severe tissue damage in mycobacterial infection while redox status was reported to be crucial in the granulomatous inflammation. Here, we used a NADPH oxidase 2 (NOX2)-deficient mice (Ncf1-/-) to investigate the role of leukocyte-produced reactive oxygen species (ROS) in mycobacterium-induced granulomatous inflammation. We found poorly controlled mycobacterial proliferation, significant body weight loss, and a high mortality rate after M. marinum infection in Ncf1-/- mice. Moreover, we noticed loose and neutrophilic granulomas and higher levels of interleukin (IL)-1 β and neutrophil chemokines in Ncf1-/- mice when compared with those in wild type mice. The lack of ROS led to reduced production of IL-1 β in macrophages, whereas neutrophil elastase (NE), an abundant product of neutrophils, may potentially exert increased inflammasome-independent protease activity and lead to higher IL-1 β production. Moreover, we showed that the abundant NE and IL-1 β were present in the caseous granulomatous inflammation of human TB infection. Importantly, blocking of IL-1 β with either a specific antibody or a recombinant IL-1 receptor ameliorated the pulmonary inflammation. These findings revealed a novel role of ROS in the early pathogenesis of neutrophilic granulomatous inflammation and suggested a potential role of IL-1 blocking in the treatment of mycobacterial infection in the lung.

Original languageEnglish
Article numbere0189453
JournalPloS one
Volume12
Issue number12
DOIs
Publication statusPublished - 2017 Dec

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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