Niche-derived exosomes control Drosophila immune stress hematopoiesis

Hematopoietic stem and progenitor cells in the bone marrow ensure continuous blood cell production. Homeostasis is controlled by a specialized microenvironment termed the niche. Extracellular vesicles released by the hematopoietic niche, both under normal and stress conditions, regulate stem cell maintenance, proliferation and differentiation. Here, we show that the Drosophila hematopoietic niche in the larval immune organ, the lymph gland, releases extracellular vesicles that mediate cell communication necessary to adapt blood cell progenitor homeostasis to immune stress. In response to wasp parasitism, ROS elevation in the niche causes the release of a heterogeneous population of EVs, including exosomes, which propagate and activate non-cell autonomously the EGFR pathway in lymph gland progenitors. Niche-derived exosomes promote progenitor differentiation into lamellocytes, a blood cell type dedicated to the neutralization of the pathogen. We further show that up-regulation of the metalloproteinase Mmp1 that occurs in niche cells in response to wasp infestation is required for exosome spreading through the niche's extracellular matrix. Our work establishes the Drosophila lymph gland as a novel in vivo model to study exosome-mediated cell communication and provides new insights into how niche-derived exosomes control immune stress hematopoiesis.