Format

Send to

Choose Destination
Cell Host Microbe. 2015 Feb 11;17(2):191-204. doi: 10.1016/j.chom.2014.12.012. Epub 2015 Jan 29.

Bacterial uracil modulates Drosophila DUOX-dependent gut immunity via Hedgehog-induced signaling endosomes.

Author information

1
School of Biological Science, Seoul National University and National Creative Research Initiative Center for Symbiosystem, Seoul National University, Seoul 151-742, South Korea; Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, South Korea.
2
School of Biological Science, Seoul National University and National Creative Research Initiative Center for Symbiosystem, Seoul National University, Seoul 151-742, South Korea.
3
Department of Chemical Engineering, POSTECH, Pohang, Kyungbuk 790-784, South Korea.
4
Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul 120-752, South Korea.
5
Department of Chemical Engineering, POSTECH, Pohang, Kyungbuk 790-784, South Korea; Department of New Biology and Center for Plant Aging Research, Institute for Basic Science, DGIST, Daegu, 711-873, South Korea.
6
School of Biological Science, Seoul National University and National Creative Research Initiative Center for Symbiosystem, Seoul National University, Seoul 151-742, South Korea; Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, South Korea. Electronic address: lwj@snu.ac.kr.

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.

Comment in

PMID:
25639794
DOI:
10.1016/j.chom.2014.12.012
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center