Spatiotemporal photolabeling of neutrophil trafficking during inflammation in live zebrafish

How neutrophils traffic during inflammation in vivo remains elusive. To visualize the origin and fate of neutrophils during induction and resolution of inflammation, we established a genetically encoded photolabeling system by generating transgenic zebrafish that express a photoconvertible fluorescent reporter Dendra2 in neutrophils. Spatiotemporal photolabeling of neutrophils in vivo demonstrates that they emerge from the hematopoietic tissue in close proximity to injured tissue and repeat forward and reverse migration between the wound and the vasculature. Subsequently, neutrophils disperse throughout the body as wound-healing proceeds, contributing to local resolution at injured tissue and systemic dissemination of wound-sensitized neutrophils. Tissue damage also alters the fate of neutrophils in the caudal hematopoietic tissue and promotes caudorostral mobilization of neutrophils via the circulation to the cephalic mesenchyme. This work provides new insight into neutrophil behaviors during inflammation and resolution within a multicellular organism.