A Glutamate-Dependent Redox System in Blood Cells Is Integral for Phagocytosis in Drosophila melanogaster

Glutamate transport is highly regulated as glutamate directly acts as a neurotransmitter [1-3] and indirectly regulates the synthesis of antioxidants [4, 5]. Although glutamate deregulation has been repeatedly linked to serious human diseases such as HIV infection and Alzheimer's [6-8], glutamate's role in the immune system is still poorly understood. We find that a putative glutamate transporter in Drosophila melanogaster, polyphemus (polyph), plays an integral part in the fly's immune response. Flies with a disrupted polyph gene exhibit decreased phagocytosis of microbial-derived bioparticles. When infected with S. aureus, polyph flies show an increase in both susceptibility and bacterial growth. Additionally, the expression of two known glutamate transporters, gender-blind and excitatory amino acid transporter 1, in blood cells affects the flies' ability to phagocytose and survive after an infection. Consistent with previous data showing a regulatory role for glutamate transport in the synthesis of the major antioxidant glutathione, polyph flies produce more reactive oxygen species (ROS) as compared to wild-type flies when exposed to S. aureus. In conclusion, we demonstrate that a polyph-dependent redox system in blood cells is necessary to maintain the cells' immune-related functions. Furthermore, our model provides insight into how deregulation of glutamate transport may play a role in disease.