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.
Keywords: Drosophila melanogaster; Hemolectin; JAK/STAT; Peroxidasin; insulin signaling; plasmatocytes; upd3.
Copyright © 2020 Shin, Cha, Koranteng, Cho and Shim.
Drosophila hemolectin gene is expressed in embryonic and larval hemocytes and its knock down causes bleeding defects.Dev Biol. 2003 Dec 15;264(2):582-91. doi: 10.1016/j.ydbio.2003.06.001. Dev Biol. 2003. PMID: 14651939
Lineage tracing of lamellocytes demonstrates Drosophila macrophage plasticity.PLoS One. 2010 Nov 19;5(11):e14051. doi: 10.1371/journal.pone.0014051. PLoS One. 2010. PMID: 21124962 Free PMC article.
Adult Drosophila Lack Hematopoiesis but Rely on a Blood Cell Reservoir at the Respiratory Epithelia to Relay Infection Signals to Surrounding Tissues.Dev Cell. 2019 Dec 16;51(6):787-803.e5. doi: 10.1016/j.devcel.2019.10.017. Epub 2019 Nov 14. Dev Cell. 2019. PMID: 31735669
The roles of JAK/STAT signaling in Drosophila immune responses.Immunol Rev. 2004 Apr;198:72-82. doi: 10.1111/j.0105-2896.2004.0133.x. Immunol Rev. 2004. PMID: 15199955 Review.
Drosophila blood cells.Cell Microbiol. 2003 Sep;5(9):573-80. doi: 10.1046/j.1462-5822.2003.00302.x. Cell Microbiol. 2003. PMID: 12925127 Review.