Selective autophagy tolerates symbiotic bacteria in the Drosophila intestine.

Hiroki Nagai, Tamaki Yano

Autophagy 2021 Apr

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Intestinal epithelium functions as a barrier to protect the host from environmental microbes. Defects in macroautophagy/autophagy combined with intestinal microbes cause a disruption of homeostasis of the tissue, which is associated with the etiology of Crohn disease, an inflammatory bowel disease. However, the molecular mechanism of how autophagy interacts with microbes in the pathology are mostly unrevealed. Our recent findings using Drosophila as a model system showed that autophagy in enterocytes suppresses a regenerative response triggered by reactive oxygen species (ROS) secreted by the host epithelia toward commensal bacteria in the intestine. Without this suppression, accumulation of a receptor protein of selective autophagy, ref(2)P, continuously acts as a signaling platform to cause excessive regeneration via cytokine production by yki (yorkie) activation. This chronic response leads to the acceleration of age-dependent barrier dysfunction, systemic inflammation, and shorter lifespan. These results uncover a novel regulatory network linking commensal bacteria, autophagy, and gut homeostasis, represented by ROS, ref(2)P, and the hippo pathway.