Circulating blood cells function as a surveillance system for damaged tissue in Drosophila larvae

Abstract

Insects have an open circulatory system in which the heart pumps blood (hemolymph) into the body cavity, where it directly bathes the internal organs and epidermis. The blood contains free and tissuebound immune cells that function in the inflammatory response. Here, we use live imaging of transgenic Drosophila larvae with fluorescently labeled blood cells (hemocytes) to investigate the circulatory dynamics of larval blood cells and their response to tissue injury. We find that, under normal conditions, the free cells rapidly circulate, whereas the tissue-bound cells are sessile. After epidermal wounding, tissue-bound cells around the wound site remain sessile and unresponsive, whereas circulating cells are rapidly recruited to the site of damage by adhesive capture. After capture, these cells distribute across the wound, appear phagocytically active, and are subsequently released back into circulation by the healing epidermis. The results demonstrate that circulating cells function as a surveillance system that monitors larval tissues for damage, and that adhesive capture, an important mechanism of recruitment of circulating cells to inflammatory sites in vertebrates, is shared by insects and vertebrates despite the vastly different architectures of their circulatory systems.adhesion ͉ inflammation ͉ live-imaging ͉ wound healing

Differential Roles of Macrophages in Diverse Phases of Skin Repair

“…Across different species, this event requires a complex and dynamic interplay of epithelial and mesenchymal cells in concert with tissue-resident and recruited hematopoetic cells to accomplish the sequential phases of the repair response: inflammation, tissue formation, and maturation (1)(2)(3)(4). The early stage of the repair response is dominated by the inflammatory phase, which is characterized by local activation of the innate immune system, resulting in an immediate influx of polymorphonuclear leukocytes (neutrophils) followed by subsequent invasion of blood monocytes, which differentiate into tissue macrophages.…”

Epithelial delamination and migration

“…The appearance of ample vacuoles in their cytoplasm clearly indicates they become phagocytically active to clear the wound site before being released back into circulation. 30 This process resembles the early response of blood cells to damaged tissue in vertebrates.…”

“…These cells belong mostly to the free circulating population, as revealed by live imaging studies using fluorescently labeled hemocytes. 30 Indeed, tissue-bound cells even when in a close range to the wound remain sessile and completely unresponsive to the injury. Once recruited at the wound site, hemocytes spread across the damaged surface and assume an adhesive morphology.…”

“…30 Free circulating cells slowly flow, in a posterior direction within an open larval body cavity while are actively pumped through the heart and run much faster in the anterior direction.…”

Active cop, passive cop: Developmental stage-specific modes of wound-induced blood cell recruitment in Drosophila

“…To investigate the inflammatory mechanism in larvae we also turned to live imaging. 10 Real time movies of blood cell circulation revealed distinct populations of tissue-bound and circulating blood cells (summarized in Fig. 1C).…”