Role of p40phox in host defense against Citrobacter rodentium infection
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 u...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-05-01
|
| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.13155 |
| _version_ | 1797374885703450624 |
|---|---|
| author | Yanyun Yan Yali Li Meili Lv Weifen Li Hai Ning Shi |
| author_facet | Yanyun Yan Yali Li Meili Lv Weifen Li Hai Ning Shi |
| author_sort | Yanyun Yan |
| collection | DOAJ |
| description | 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 p40phox, 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 p40phox 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 p40phox−/− and wild‐type mice. Interestingly, higher IL‐10 levels were observed in the supernatants of MLN cells and splenocytes isolated from infected p40phox‐deficient mice. Further, a higher expression level of inducible nitric oxide synthase (iNOS) was also noted in mice lacking p40phox. In contrast to wild‐type mice, p40phox−/− mice exhibited greater NO production after LPS or bacterial antigen re‐stimulation. These results suggest that p40phox−/− 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. |
| first_indexed | 2024-03-08T19:12:12Z |
| format | Article |
| id | doaj.art-0951ea51226a42aaaa2beeb8225a1ee0 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-03-08T19:12:12Z |
| publishDate | 2021-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-0951ea51226a42aaaa2beeb8225a1ee02023-12-27T09:30:57ZengWileyFEBS Open Bio2211-54632021-05-011151476148610.1002/2211-5463.13155Role of p40phox in host defense against Citrobacter rodentium infectionYanyun Yan0Yali Li1Meili Lv2Weifen Li3Hai Ning Shi4Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation College of Life Sciences Hunan Normal University Changsha ChinaHunan Provincial Key Laboratory of Animal Intestinal Function and Regulation College of Life Sciences Hunan Normal University Changsha ChinaSichuan University Chengdu ChinaZhejiang University Hangzhou ChinaMucosal Immunology and Biology Research Center Harvard Medical School Massachusetts General Hospital Charlestown MA USANADPH 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 p40phox, 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 p40phox 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 p40phox−/− and wild‐type mice. Interestingly, higher IL‐10 levels were observed in the supernatants of MLN cells and splenocytes isolated from infected p40phox‐deficient mice. Further, a higher expression level of inducible nitric oxide synthase (iNOS) was also noted in mice lacking p40phox. In contrast to wild‐type mice, p40phox−/− mice exhibited greater NO production after LPS or bacterial antigen re‐stimulation. These results suggest that p40phox−/− 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.https://doi.org/10.1002/2211-5463.13155C. rodentiumcolonic inflammationIBDp40phox |
| spellingShingle | Yanyun Yan Yali Li Meili Lv Weifen Li Hai Ning Shi Role of p40phox in host defense against Citrobacter rodentium infection FEBS Open Bio C. rodentium colonic inflammation IBD p40phox |
| title | Role of p40phox in host defense against Citrobacter rodentium infection |
| title_full | Role of p40phox in host defense against Citrobacter rodentium infection |
| title_fullStr | Role of p40phox in host defense against Citrobacter rodentium infection |
| title_full_unstemmed | Role of p40phox in host defense against Citrobacter rodentium infection |
| title_short | Role of p40phox in host defense against Citrobacter rodentium infection |
| title_sort | role of p40phox in host defense against citrobacter rodentium infection |
| topic | C. rodentium colonic inflammation IBD p40phox |
| url | https://doi.org/10.1002/2211-5463.13155 |
| work_keys_str_mv | AT yanyunyan roleofp40phoxinhostdefenseagainstcitrobacterrodentiuminfection AT yalili roleofp40phoxinhostdefenseagainstcitrobacterrodentiuminfection AT meililv roleofp40phoxinhostdefenseagainstcitrobacterrodentiuminfection AT weifenli roleofp40phoxinhostdefenseagainstcitrobacterrodentiuminfection AT hainingshi roleofp40phoxinhostdefenseagainstcitrobacterrodentiuminfection |