| First Author | Chao WC | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 12 | Pages | e0189453 |
| PubMed ID | 29228045 | Mgi Jnum | J:252559 |
| Mgi Id | MGI:6103656 | Doi | 10.1371/journal.pone.0189453 |
| Citation | Chao WC, et al. (2017) Mycobacterial infection induces higher interleukin-1beta and dysregulated lung inflammation in mice with defective leukocyte NADPH oxidase. PLoS One 12(12):e0189453 |
| abstractText | 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)-1beta and neutrophil chemokines in Ncf1-/- mice when compared with those in wild type mice. The lack of ROS led to reduced production of IL-1beta in macrophages, whereas neutrophil elastase (NE), an abundant product of neutrophils, may potentially exert increased inflammasome-independent protease activity and lead to higher IL-1beta production. Moreover, we showed that the abundant NE and IL-1beta were present in the caseous granulomatous inflammation of human TB infection. Importantly, blocking of IL-1beta 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. |
