Autophagy degrades cytoplasmic components and is important for development and human health. Although autophagy is known to be influenced by systemic intercellular signals, the proteins that control autophagy are largely thought to function within individual cells. Here, we report that Drosophila macroglobulin complement-related (Mcr), a complement ortholog, plays an essential role during developmental cell death and inflammation by influencing autophagy in neighboring cells. This function of Mcr involves the immune receptor Draper, suggesting a relationship between autophagy and the control of inflammation. Interestingly, Mcr function in epithelial cells is required for macrophage autophagy and migration to epithelial wounds, a Draper-dependent process. This study reveals, unexpectedly, that complement-related from one cell regulates autophagy in neighboring cells via an ancient immune signaling program. Display omitted •Macroglobulin complement-related (Mcr) functions in salivary gland cell death•Mcr regulates cell death by influencing autophagy in neighboring cells•Mcr is required in epithelial cells for macrophage migration to epithelial wounds•Mcr function in epithelial cells is required for macrophage autophagy A complement ortholog in Drosophila plays an essential role during developmental cell death and inflammation by influencing autophagy in neighboring cells.