A nonsecretory antimicrobial peptide mediates inflammatory organ damage in Drosophila renal tubules.

An excessive immune response damages organs, yet its molecular mechanism is incompletely understood. Here, we screened a factor mediating organ damage upon genetic activation of the innate immune pathway using Drosophila renal tubules. We found that an antimicrobial peptide, Attacin-D (AttD), causes organ damage upon immune deficiency (Imd) pathway activation in the Malpighian tubules. Loss of AttD function suppresses most of the pathological phenotypes induced by Imd activation, such as cell death, bloating of the whole animal, and mortality, without compromising the immune activation. AttD is required for the immune-induced damage specifically in the Malpighian tubules and not the midgut. Unlike other antimicrobial peptides, AttD lacks a signal peptide and stays inside tubular cells, potentially damaging the tubular cells via aggregation and oligomerization. Suppression of AttD almost completely attenuates the pathology caused by a gut-tumor-induced immune activation. Our study elucidates the mechanistic effector of immune-induced organ damage.