Role of xanthine dehydrogenase and aging on the innate immune response of Drosophila.

It has been proposed that uric acid is an important scavenger of deleterious oxygen species and peroxynitrite in biological systems. The cellular sources responsible for the generation of damage-causing reactive oxygen species (ROS) are widespread. Xanthine dehydrogenase (XDH) / oxidase (XOD) catalyzes the oxidation of xanthine to uric acid. The rosy (ry) gene encodes XDH/XOD in Drosophila melanogaster. XDH codes for uric acid which is a ROS scavenger. XOD however is an enzyme system implicated in ROS production. In this study, we investigated the roles of XDH in the fly's immune defense response to infection and in the aging process. We first compared ROS generation and nitric oxide (NO) level in the whole body and the gut of XDH mutant with those of wild type. Our results suggested that XDH has a protective effect with respect to both ROS and NO generations, particularly in the gut. We also examined the effect of a XDH deletion mutant on the relative sensitivity of the organism against bacterial infection, on the immune inducibility of antimicrobial peptides and on the effect of aging in the defensive response to infection. Our results strongly suggest that XDH plays an important role in the innate immune response and that the age-associated deterioration of the innate immune response might be, at least in part, associated with the loss of XDH activity in the aging process.