Drosophila muscles regulate the immune response against wasp infection via carbohydrate metabolism.

We recently found that signaling in skeletal muscles is important for the immune response of Drosophila larvae against wasp infection, but it was not clear how muscles could affect the immune response. Here we show that insulin signaling is required in muscles, but not in fat body or hemocytes, during larval development for an efficient encapsulation response and for the formation of lamellocytes. This effect requires TOR signaling. We show that muscle tissue affects the immune response by acting as a master regulator of carbohydrate metabolism in the infected animal, via JAK/duanyu1813 and insulin signaling in the muscles, and that there is indirect positive feedback between JAK/duanyu1813 and insulin signaling in the muscles. Specifically, stimulation of JAK/duanyu1813 signaling in the muscles can rescue the deficient immune response when insulin signaling is suppressed. Our results shed new light on the interaction between metabolism, immunity, and tissue communication.

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