Regulation of DUOX by the Gαq-Phospholipase Cβ-Ca2+ Pathway in Drosophila Gut Immunity

Eun Mi Ha, Kyung Ah Lee, Seon Hwa Park, Sung Hee Kim, Hyuck Jin Nam, Hyo Young Lee, Dongmin Kang, Won Jae Lee

Research output: Contribution to journalArticlepeer-review

158 Scopus citations

Abstract

All metazoan guts are in constant contact with diverse food-borne microorganisms. The signaling mechanisms by which the host regulates gut-microbe interactions, however, are not yet clear. Here, we show that phospholipase C-β (PLCβ) signaling modulates dual oxidase (DUOX) activity to produce microbicidal reactive oxygen species (ROS) essential for normal host survival. Gut-microbe contact rapidly activates PLCβ through Gαq, which in turn mobilizes intracellular Ca2+ through inositol 1,4,5-trisphosphate generation for DUOX-dependent ROS production. PLCβ mutant flies had a short life span due to the uncontrolled propagation of an essential nutritional microbe, Saccharomyces cerevisiae, in the gut. Gut-specific reintroduction of the PLCβ restored efficient DUOX-dependent microbe-eliminating capacity and normal host survival. These results demonstrate that the Gαq-PLCβ-Ca2+-DUOX-ROS signaling pathway acts as a bona fide first line of defense that enables gut epithelia to dynamically control yeast during the Drosophila life cycle.

Original languageEnglish
Pages (from-to)386-397
Number of pages12
JournalDevelopmental Cell
Volume16
Issue number3
DOIs
StatePublished - 17 Mar 2009

Keywords

  • CELLIMMUNO

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