Effects of low concentrations of arsenic on the innate immune system of the zebrafish (Danio rerio)

Arsenic has been associated with a multitude of human health problems; however, its impact on host resistance to infection has not been extensively researched. In vertebrates, the innate immune response is vital for potentiating the adaptive immune response. Therefore, dampening of the innate immune response results in an immunocompromised host. In this present study, effects of low concentrations of arsenic on zebrafish resistance to infection are evaluated. Exposure to 2 and 10 ppb arsenic, both considered safe levels in drinking water, resulted in a greater than 50-fold increase in viral load and at least a 17-fold increase in bacterial load in embryos. To determine the cause of this amplified pathogen load, important components of the innate immune system were analyzed. Presence of arsenic dampened the overall innate immune health of the fish as evidenced by reductions in respiratory burst activity. Viral infection, after arsenic exposure, showed decreases of up to 13- and 1.5-fold changes in interferon and Mx mRNA expression, respectively. Bacterial infection, post arsenic exposure, demonstrated at least 2.5- and 4-fold declines in interleukin-1 beta and tumor necrosis factor-alpha mRNA levels, respectively. Maximum expression of these essential cytokines was also delayed upon arsenic exposure. Our data indicate that arsenic exposure, at concentrations deemed safe in drinking water, suppresses the overall innate immune function in zebrafish and present the zebrafish as a unique model for studying immunotoxicity of environmental toxicants. To our knowledge, this is the first report describing the effects of such low levels of arsenic on host resistance to infection.