EFFECT OF DIETARY INDUCED OXIDATIVE STRESS ON INTESTINAL PHYSIOLOGY AND THE DEVELOPMENT OF MUCOSAL IMMUNITY TO ENTERIC PATHOGENS

1)Develop mouse models of orally-acquired enteric viral and food-borne bacterial infections to assess the effect of nutritionally-induced oxidative stress on the pathogenesis of enteric infections. 2)Determine the effect of dietary-induced oxidative stress on the pathogenesis of enteric viral and bacterial infections of the GI tract. 3)Determine the parameters of innate and acquired mucosal immunity, and GI function that are altered by oxidative stress. 4)Map the redistribution of trace elements important for GI and immune function, and resistance to oxidative stress that are altered by diet and enteric infections. 5)Determine the mechanism(s) by which oxidative stress alters intestinal physiology and immunity to intestinal pathogens by a) examining changes in the redox state that affect specific signal transduction and gene activation pathways related to GI and immune function, and b) assessing whether selection of mutated strains of virus or bacteria with altered pathogenicity occurs under conditions of oxidative stress.