Sequential activation of NFkB, JNK, and cytokine signaling in the Drosophila blood system in response to distal injury

In mammals, injury-induced inflammation is mediated by Toll-like receptor (TLR)/NF-κB signaling in blood cells. Although Toll signaling is conserved in Drosophila, how the blood system senses and responds to injury remains largely unknown. By contrast, Toll pathway activation in the context of humoral immunity has been well characterized in Drosophila, focusing primarily on the adult fat body. In this study, we show that epidermal injury in Drosophila larvae causes rapid activation of Toll signaling in blood cells, and is largely independent of the pathway that is known to activate Toll in response to infection. We also show that Jun kinase signaling is activated by injury rapidly under control of Toll signaling, but only Toll contribute to the delayed downstream activation of cytokine-like signaling. It has been previously shown that epidermal injury causes blood cell differentiation in Drosophila; however the underlying molecular mechanism was unknown. Our work demonstrates that Toll and cytokine-like (JAK/STAT) signaling are required sequentially for injury-induced blood cell differentiation. Future studies aiming at understanding how epidermal injury initiates signals that leads to Toll activation may be of specific relevance to similar scenarios in mammalian injury responses