KIM, CH; University of Maine: The Role of Arsenic in Modulating Innate Immunity in the Zebrafish

The innate immune response constitutes the first line of defense against invading pathogens and can be perturbed by environmental toxicants such as arsenic. Arsenic is a metalloid toxicant that is present in many toxic waste sites and can accumulate in groundwater and well water. Exposures to such non toxic levels of arsenic have been associated with various human diseases including skin and internal cancers, diabetes mellitus, and atherosclerotic diseases. In addition, arsenic compounds have also been shown to modulate the innate immune response by altering phagocytic activity, inhibiting clearance of bacteria from the infected host, and perturbing cytokine regulation. This study reports the effects of the environmental toxicant, arsenic, on the innate immunity of the zebrafish, Danio rerio. The small size and short generation time of the zebrafish, combined with the sequenced genome and the knowledge of developmental processes, have made the zebrafish an ideal model to study the effects of environmental toxicants such as arsenic. We have found that respiratory burst activity and TNF-&alpha expression are decreased by arsenic exposure, and that arsenic reduces Mx expression, but enhances type I interferon (IFN) expression over time. Arsenic also decreases induction and alters the kinetics of IFN and Mx expression in virus-infected zebrafish. We have extended these studies by examining perturbations in other innate immune factors, including respiratory burst activity, mRNA expression of components of the Toll Signal Transduction pathway, cytokines, Iinflammatory factors, and resistance to pathogen challenge in arsenic-exposed zebrafish larvae.