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.