Role of p40phox in host defense against Citrobacterrodentium infection. Issue 5 (9th April 2021)

• Record Type: Journal Article
• Authors: Yan, Yanyun; Li, Yali; Lv, Meili; Li, Weifen; Shi, Hai Ning
• Editors: Castrillo Viguera, Antonio
• Is Part Of: FEBS open bio. Volume 11:Issue 5(2021)
• Page Start: 1476
• Page End: 1486
• Publication Date: 2021-04-09
• Subjects: C. rodentium -- colonic inflammation -- IBD -- p40phox; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.13155
• Languages: English
• ISSNs: 2211-5463

Abstract

Abstract : NADPH oxidase (NOX) is a membrane‐bound enzyme complex that generates reactive oxygen species (ROS). Mutations in NOX subunit genes have been implicated in the pathogenesis of inflammatory bowel disease (IBD), indicating a crucial role for ROS in regulating host immune responses. In this study, we utilize genetically deficient mice to investigate whether defects in p40 phox, one subunit of NOX, impair host immune response in the intestine and aggravate disease in an infection‐based ( Citrobacter rodentium ) model of colitis. We show that p40 phox deficiency does not increase susceptibility of mice to C. rodentium infection, as no differences in body weight loss, bacterial clearance, colonic pathology, cytokine production, or immune cell recruitment were observed between p40 phox −/− and wild‐type mice. Interestingly, higher IL‐10 levels were observed in the supernatants of MLN cells and splenocytes isolated from infected p40 phox ‐deficient mice. Further, a higher expression level of inducible nitric oxide synthase (iNOS) was also noted in mice lacking p40 phox . In contrast to wild‐type mice, p40 phox −/− mice exhibited greater NO production after LPS or bacterial antigen re‐stimulation. These results suggest that p40 phox −/− mice do not develop worsened colitis. While the precise mechanisms are unclear, it may involve the observed alteration in cytokine responses and enhancement in levels of iNOS and NO. Abstract : We investigated the role of p40 phox in Citrobacter rodentium infection. Although p40 phox −/− mice did not develop worsened colitis, higher IL‐10 levels were observed in MLN cells and splenocytes isolated from infected p40 phox −/− mice compared with wild‐type mice. Further, higher expression level of iNOS and greater NO production was noted in p40 phox −/− lymphocytes after LPS or bacterial antigen re‐stimulation.