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Bacterial Uracil Modulates Drosophila DUOX-Dependent Gut Immunity via Hedgehog-Induced Signaling Endosomes

Title
Bacterial Uracil Modulates Drosophila DUOX-Dependent Gut Immunity via Hedgehog-Induced Signaling Endosomes
Authors
Lee, KA[Lee, Kyung-Ah]Kim, B[Kim, Boram]Bhin, J[Bhin, Jinhyuk]Kim, DH[Kim, Do Hun]You, H[You, Hyejin]Kim, EK[Kim, Eun-Kyoung]Kim, SH[Kim, Sung-Hee]Ryu, JH[Ryu, Ji-Hwan]Hwang, D[Hwang, Daehee]Lee, WJ[Lee, Won-Jae]
DGIST Authors
Hwang, D[Hwang, Daehee]
Issue Date
2015-02-11
Citation
Cell Host and Microbe, 17(2), 191-204
Type
Article
Article Type
Article
ISSN
1931-3128
Abstract
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 PLC beta/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.
URI
http://hdl.handle.net/20.500.11750/2609
DOI
10.1016/j.chom.2014.12.012
Publisher
Cell Press
Related Researcher
  • Author Hwang, Dae Hee Systems Biology and Medicine Lab
  • Research Interests Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
Files:
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Collection:
New BiologyETC1. Journal Articles


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