assessing-cellular-immune-response-fruit-fly-drosophila-melanogaster

Assessing the Cellular Immune Response of the Fruit Fly, <em>Drosophila melanogaster</em>, Using an In Vivo Phagocytosis Assay

In all animals, innate immunity provides an immediate and robust defense against a broad spectrum of pathogens. Humoral and cellular immune responses are ...

University of Maryland

Glutamate transport is highly regulated as glutamate directly acts as a neurotransmitter and indirectly regulates the synthesis of antioxidants. Although glutamate deregulation has been repeatedly linked to serious human diseases such as HIV infection and Alzheimer's, 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, genderblind 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.

A glutamate-dependent redox system in blood cells is integral for phagocytosis in Drosophila melanogaster.

The uptake and destruction of bacteria by phagocytic cells is an essential defense mechanism in metazoans. To identify novel genes involved in the phagocytosis of , a major human pathogen, we assessed the phagocytic capacity of adult blood cells (hemocytes) of the fruit fly,  by testing several lines of the Drosophila Genetic Reference Panel. Natural genetic variation in the gene  () correlated with low phagocytic capacity in hemocytes, pointing to Rbfox1 as a candidate regulator of phagocytosis. Loss of Rbfox1 resulted in increased expression of the Ig superfamily member  (). Silencing of  in Rbfox1-depleted blood cells rescued the fly's cellular immune response to , indicating that downregulation of  by Rbfox1 is critical for  phagocytosis in  To our knowledge, this study is the first to demonstrate a link between  and host defense against .

Article	Year
A glutamate-dependent redox system in blood cells is integral for phagocytosis in Drosophila melanogaster. Current biology : CB\| PubMed ID: 24210616	2013
The Splicing Factor Mediates the Cellular Immune Response in . Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 29997126	2018

Ashley E. Nazario-Toole

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