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Drosophila  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  Drosophila  larvae. Here, we show that larval plasmatocytes exhibit differential expressions of  Hemolectin (Hml)  and  Peroxidasin (Pxn)  during development. Moreover, removal of plasmatocytes by overexpressing pro-apoptotic genes,  hid  and  reaper  in  Hml -positive plasmatocytes, feeding high sucrose diet, or wasp infestation results in increased circulating hemocytes that are  Hml -negative. Interestingly these  Hml -negative plasmatocytes retain  Pxn  expression, and animals expressing  Hml -negative and  Pxn -positive subtype largely attenuate growth and abrogate metabolism. Furthermore, elevated levels of a cytokine,  unpaired 3 , are detected when  Hml -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  upd3 . Overall, this study highlights heterogeneity in  Drosophila  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.

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