Cited time in webofscience Cited time in scopus

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
Author(s)
Lee, Kyung-AhKim, BoramBhin, JinhyukKim, Do HunYou, HyejinKim, Eun-KyoungKim, Sung-HeeRyu, Ji-HwanHwang, DaeheeLee, Won-Jae
Issued Date
2015-02
Citation
Cell Host and Microbe, v.17, no.2, pp.191 - 204
Type
Article
Keywords
CADHERIN CAD99CDUAL OXIDASEMICROBIOTAHOMEOSTASISCOMMENSALPATHWAYMELANOGASTERDYSBIOSISHEALTHMODEL
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 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.
URI
http://hdl.handle.net/20.500.11750/2609
DOI
10.1016/j.chom.2014.12.012
Publisher
Cell Press
Files in This Item:

There are no files associated with this item.

Appears in Collections:
Department of New Biology Systems Biology and Medicine Lab 1. Journal Articles

qrcode

  • twitter
  • facebook
  • mendeley

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE