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Bacterial Uracil Modulates Drosophila DUOX-Dependent Gut Immunity via Hedgehog-Induced Signaling Endosomes
- Bacterial Uracil Modulates Drosophila DUOX-Dependent Gut Immunity via Hedgehog-Induced Signaling Endosomes
- Lee, Kyung-Ah; Kim, Boram; Bhin, Jinhyuk; Kim, Do Hun; You, Hyejin; Kim, Eun-Kyoung; Kim, Sung-Hee; Ryu, Ji-Hwan; Hwang, Daehee; Lee, Won-Jae
- DGIST Authors
- Hwang, Daehee
- Issue Date
- Cell Host and Microbe, 17(2), 191-204
- Article Type
- Genetic studies in Drosophila have demonstrated that generation of microbicidal reactive oxygen species (ROS) through the NADPH dual oxidase (DUOX) is a first line of defense in the gut epithelia. Bacterial uracil acts as DUOX-activating ligand through poorly understood mechanisms. Here, we show that the Hedgehog (Hh) signaling pathway modulates uracil-induced DUOX activation. Uracil-induced Hh signaling is required for intestinal expression of the calcium-dependent cell adhesion molecule Cadherin 99C (Cad99C) and subsequent Cad99C-dependent formation of endosomes. These endosomes play essential roles in uracil-induced ROS production by acting as signaling platforms for PLCβ/PKC/Ca2+-dependent DUOX activation. Animals with impaired Hh signaling exhibit abolished Cad99C-dependent endosome formation and reduced DUOX activity, resulting in high mortality during enteric infection. Importantly, endosome formation, DUOX activation, and normal host survival are restored by genetic reintroduction of Cad99C into enterocytes, demonstrating the important role for Hh signaling in host resistance to enteric infection. © 2015 Elsevier Inc.
- Cell Press
- Related Researcher
Hwang, Dae Hee
Systems Biology and Medicine Lab
Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
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- Department of New BiologySystems Biology and Medicine Lab1. Journal Articles
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