A Nonsecretory Antimicrobial Peptide Mediates Inflammatory Organ Damage inDrosophilaRenal Tubules

Summary An excessive immune response damages organs, yet its molecular mechanism is incompletely understood. In this study, we used Drosophila renal tubules as a model to screen a factor mediating organ damage upon genetic activation of an innate immune Imd signalling pathway. We identified an antimicrobial peptide, Attacin-D (AttD), which causes organ damage upon Imd activation in the Malpighian tubules. Loss of AttD function suppresses most of the pathological phenotypes induced by Imd activation, such as cell death, compensatory stem cell proliferation, bloating of whole animal, susceptibility to a high salt diet, elevation of purine levels, and mortality, without compromising the immune activation. AttD is required for the immune-induced damage specifically in the Malpighian tubules but not the midgut. Interestingly, AttD uniquely lacks the signal peptide and is not secreted out from cells. Suppression of AttD almost completely attenuates mortality induced by gut tumour-induced immune activation. Our study elucidates the mechanistic effector of immune-induced organ damage.