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Bacterial-Derived Uracil as a Modulator of Mucosal Immunity and Gut-Microbe Homeostasis in Drosophila

Authors
 Kyung-Ah Lee  ;  Sung-Hee Kim  ;  Eun-Kyoung Kim  ;  Eun-Mi Ha  ;  Hyejin You  ;  Boram Kim  ;  Min-Ji Kim  ;  Youngjoo Kwon  ;  Ji-Hwan Ryu  ;  Won-Jae Lee 
Citation
 CELL, Vol.153(4) : 797-811, 2013 
Journal Title
 CELL 
ISSN
 0092-8674 
Issue Date
2013
MeSH
Animals ; Drosophila/immunology* ; Drosophila/microbiology* ; Gastrointestinal Tract/immunology ; Gastrointestinal Tract/microbiology ; Gastrointestinal Tract/physiology ; Homeostasis ; Humans ; Immunity, Mucosal* ; Inflammation/immunology ; Inflammation/microbiology ; Inflammatory Bowel Diseases/immunology ; Inflammatory Bowel Diseases/microbiology ; NADPH Oxidases/metabolism ; Pectobacterium carotovorum/physiology* ; Reactive Oxygen Species/metabolism ; Stem Cells/metabolism ; Symbiosis* ; Uracil/metabolism*
Keywords
Animals ; Drosophila/immunology* ; Drosophila/microbiology* ; Gastrointestinal Tract/immunology ; Gastrointestinal Tract/microbiology ; Gastrointestinal Tract/physiology ; Homeostasis ; Humans ; Immunity, Mucosal* ; Inflammation/immunology ; Inflammation/microbiology ; Inflammatory Bowel Diseases/immunology ; Inflammatory Bowel Diseases/microbiology ; NADPH Oxidases/metabolism ; Pectobacterium carotovorum/physiology* ; Reactive Oxygen Species/metabolism ; Stem Cells/metabolism ; Symbiosis* ; Uracil/metabolism*
Abstract
All metazoan guts are subjected to immunologically unique conditions in which an efficient antimicrobial system operates to eliminate pathogens while tolerating symbiotic commensal microbiota. However, the molecular mechanisms controlling this process are only partially understood. Here, we show that bacterial-derived uracil acts as a ligand for dual oxidase (DUOX)-dependent reactive oxygen species generation in Drosophila gut and that the uracil production in bacteria causes inflammation in the gut. The acute and controlled uracil-induced immune response is required for efficient elimination of bacteria, intestinal cell repair, and host survival during infection of nonresident species. Among resident gut microbiota, uracil production is absent in symbionts, allowing harmonious colonization without DUOX activation, whereas uracil release from opportunistic pathobionts provokes chronic inflammation. These results reveal that bacteria with distinct abilities to activate uracil-induced gut inflammation, in terms of intensity and duration, act as critical factors that determine homeostasis or pathogenesis in gut-microbe interactions
Full Text
http://www.sciencedirect.com/science/article/pii/S0092867413004509
DOI
10.1016/j.cell.2013.04.009
Appears in Collections:
5. Research Institutes (연구소) > Research Center for Human Natural Defense System (생체방어연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Min Ji(김민지)
Ryu, Ji Hwan(유지환)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/88220
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