Role of p40phox in host defense against Citrobacter rodentium infection.
Yanyun YanYali LiMeili LvWeifen LiHai Ning ShiPublished in: FEBS open bio (2021)
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.
Keyphrases
- wild type
- reactive oxygen species
- immune response
- high fat diet induced
- nitric oxide synthase
- weight loss
- magnetic resonance imaging
- dendritic cells
- inflammatory response
- dna damage
- cell death
- bariatric surgery
- magnetic resonance
- gene expression
- metabolic syndrome
- induced apoptosis
- poor prognosis
- insulin resistance
- genome wide
- dna methylation
- long non coding rna
- computed tomography
- gastric bypass
- endoplasmic reticulum stress
- anti inflammatory
- contrast enhanced