Gut immunopathology in response to Vibrio parahaemolyticus infection
University of Delaware
Vibrio parahaemolyticus is a comma shaped, Gram-negative bacterium that is present worldwide as a normal part of the marine ecosystem, and is the leading cause of bacterial seafood-related gastroenteritis. It is estimated that the majority of Vibrio spp. infections in the United States, which have increased by 76% since 2011, are caused by V. parahaemolyticus. Infection occurs 24-48 hours following the consumption of raw or undercooked shellfish. Improper handling of shellfish, oysters in particular, permits organism growth and subsequent human infection. Infection in healthy individuals is self-limiting, and involves headache, vomiting, fever, diarrhea, and chills. Typically, oral hydration is sufficient treatment, however those with chronic medical conditions are at risk for more severe infections leading to septicemia and death. It is estimated that 20% of the US population is at risk due to the presence of a chronic medical condition. Despite the risks and increase in incidence of infection, very little is known about the immune response to V. parahaemolyticus. To date, only a single study has focused on human infection with this organism. In order to elucidate the immune response to infection, a murine model was developed that mimics the orogastric route of infection. Mice are pretreated orogastrically with streptomycin to facilitate infection with V. parahaemolyticus. Infection was confirmed by daily fecal shedding and histologically by immune cell influx into colonic tissue. We hypothesized that organism clearance was dependent on a Th17-mediated adaptive immune response, leading to proinflammatory immune cell influx via IL-17 family cytokine production. Initial analysis of proinflammatory cytokine mRNA expression failed to provide clues to immune mechanisms responsible for organism clearance, however markers of innate immunity such as fecal lactoferrin and goblet cell proliferation were upregulated. In order to establish whether the Th17 response was required for infection, IL-23p19 deficient mice were infected with V. parahaemolyticus, as they are incapable of mounting a Th17 response. Interestingly, these mice displayed reduced organism retention as compared to genetically intact controls. Here we conclude alternative immune pathways may be more efficient at organism clearance, and further investigation will be required.