Hypoxia exacerbates intestinal injury and inflammatory response mediated by myeloperoxidase during Salmonella Typhimurium infection in mice

BACKGROUND: High-altitude exposure can cause oxidative stress damage in the intestine, which leads to increased intestinal permeability and bacterial translocation, resulting in local and systemic inflammation. Control of infection is critically dependent on the host’s ability to kill pathogens with reactive oxygen species (ROS). Myeloperoxidase (MPO) targets ROS in pathogens. This study aimed to investigate the effects of hypoxia on the colonic mucosal barrier and myeloperoxidase (MPO)-mediated innate immune response in the colon. METHODS AND RESULTS: Genetically engineered mice were exposed to a hypobaric oxygen chamber for 3 days and an inflammation model was established using Salmonella Typhimurium infection. We found that hypoxic exposure caused the development of exacerbated bacterial colitis and enhanced bacterial dissemination in MPO-deficient mice. Infection and disease severity were associated with significantly increased Ly6G(+) neutrophil and F4/80(+) macrophage counts in infected tissues, which is consistent with elevated proinflammatory cytokines and chemoattractant molecules. Hypoxia restrained antioxidant ability and MPO deficiency aggravated the respiratory burst in the colon. CONCLUSION: Hypoxia can damage the colonic mucosa. MPO mediates the innate immune response and regulates the mucosal and systemic inflammatory responses to Salmonella infection during hypoxia.