AUTHOR=Shin Mingyu , Cha Nuri , Koranteng Ferdinand , Cho Bumsik , Shim Jiwon 

TITLE=Subpopulation of Macrophage-Like Plasmatocytes Attenuates Systemic Growth via JAK/STAT in the Drosophila Fat Body

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00063

DOI=10.3389/fimmu.2020.00063

ISSN=1664-3224

ABSTRACT=<p><italic>Drosophila</italic> hemocytes, like those of mammals, are given rise from two distinctive phases during both the embryonic and larval hematopoiesis. Embryonically derived hemocytes, mostly composed of macrophage-like plasmatocytes, are largely identified by genetic markers. However, the cellular diversity and distinct functions of possible subpopulations within plasmatocytes have not been explored in <italic>Drosophila</italic> larvae. Here, we show that larval plasmatocytes exhibit differential expressions of <italic>Hemolectin (Hml)</italic> and <italic>Peroxidasin (Pxn)</italic> during development. Moreover, removal of plasmatocytes by overexpressing pro-apoptotic genes, <italic>hid</italic> and <italic>reaper</italic> in <italic>Hml</italic>-positive plasmatocytes, feeding high sucrose diet, or wasp infestation results in increased circulating hemocytes that are <italic>Hml</italic>-negative. Interestingly these <italic>Hml</italic>-negative plasmatocytes retain <italic>Pxn</italic> expression, and animals expressing <italic>Hml</italic>-negative and <italic>Pxn</italic>-positive subtype largely attenuate growth and abrogate metabolism. Furthermore, elevated levels of a cytokine, <italic>unpaired 3</italic>, are detected when <italic>Hml</italic>-positive hemocytes are ablated, which in turn activates JAK/STAT activity in several tissues including the fat body. Finally, we observed that insulin signaling is inhibited in this background, which can be recovered by concurrent loss of <italic>upd3</italic>. Overall, this study highlights heterogeneity in <italic>Drosophila</italic> plasmatocytes and a functional plasticity of each subtype, which reaffirms extension of their role beyond immunity into metabolic regulation for cooperatively maintaining internal homeostatic balance.</p>