AUTHOR=Ozakman Yaprak , Eleftherianos Ioannis 

TITLE=TGF-β Signaling Interferes With the Drosophila Innate Immune and Metabolic Response to Parasitic Nematode Infection

JOURNAL=Frontiers in Physiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2019.00716

DOI=10.3389/fphys.2019.00716

ISSN=1664-042X

ABSTRACT=<p>The common fruit fly, <italic>Drosophila melanogaster</italic>, is an outstanding model to study the molecular basis of anti-pathogen immunity. The parasitic nematode <italic>Heterorhabditis gerrardi,</italic> together with its mutualistic bacteria <italic>Photorhabdus asymbiotica,</italic> infects a wide range of insects, including <italic>D. melanogaster</italic>. Recently, we have shown that transforming growth factor-β (TGF-ß) signaling in <italic>D. melanogaster</italic> is regulated in response to parasitic nematode infection. In the current study, we investigated the contribution of two TGF-ß signaling branches, the activin and the bone morphogenetic protein (BMP), to <italic>D. melanogaster</italic> immune function against <italic>H. gerrardi</italic>. We used <italic>D. melanogaster</italic> larvae carrying mutations in the genes coding for the TGF-ß extracellular ligands <italic>daw</italic> and <italic>dpp</italic>. We have demonstrated that the number of circulating hemocytes in uninfected <italic>daw</italic> and <italic>dpp</italic> mutants decreases twofold compared to background controls, yet no significant changes in hemocyte numbers and survival of the TGF-ß mutants are observed upon nematode infection. However, we have shown that nematode-infected <italic>daw</italic> mutants express <italic>Dual oxidase</italic> at higher levels and phenoloxidase activity at lower levels compared to their background controls. To elucidate the contribution of TGF-ß signaling in the metabolic response of <italic>D. melanogaster</italic> to parasitic nematodes, we estimated lipid and carbohydrate levels in <italic>daw</italic> and <italic>dpp</italic> mutant larvae infected with <italic>H. gerrardi</italic>. We have found that both nematode-infected mutants contain lipid droplets of larger size, with <italic>daw</italic> mutant larvae also containing elevated glycogen levels. Overall, our findings indicate that the regulation of activin and BMP branches of TGF-ß signaling can alter the immune and metabolic processes in <italic>D. melanogaster</italic> during response to parasitic nematode infection. Results from this study shed light on the molecular signaling pathways insects activate to regulate mechanisms for fighting potent nematode parasites, which could lead to the identification of novel management strategies for the control of damaging pests.</p>