Regulation of DUOX by the Galphaq-phospholipase Cbeta-Ca2+ pathway in Drosophila gut immunity.
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-beta (PLCbeta) signaling modulates dual oxidase (DUOX) activity to produce microbicidal reactive oxygen species (ROS) essential for normal host survival. Gut-microbe contact rapidly activates PLCbeta through Galphaq, which in turn mobilizes intracellular Ca(2+) through inositol 1,4,5-trisphosphate generation for DUOX-dependent ROS production. PLCbeta 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 PLCbeta restored efficient DUOX-dependent microbe-eliminating capacity and normal host survival. These results demonstrate that the Galphaq-PLCbeta-Ca(2+)-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.
Ha
Eun-Mi
EM
Division of Life and Pharmaceutical Science, Ewha Woman's University, Seoul 120-750, South Korea.
Lee
Kyung-Ah
KA
Park
Seon Hwa
SH
Kim
Sung-Hee
SH
Nam
Hyuck-Jin
HJ
Lee
Hyo-Young
HY
Kang
Dongmin
D
Lee
Won-Jae
WJ
D000818:Animals; D030801:Animals, Genetically Modified; D020013:Calcium Signaling; D002460:Cell Line; D004064:Digestive System / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004330:Drosophila / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism*; D007113:Immunity, Innate; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008954:Models, Biological; D019255:NADPH Oxidases / Q000378:metabolism*; D054799:Phospholipase C beta / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000276:immunology; D015398:Signal Transduction
D029721:Drosophila Proteins; D017382:Reactive Oxygen Species; C505384:dual oxidase, Drosophila; D015544:Inositol 1,4,5-Trisphosphate; D019255:NADPH Oxidases; D054799:Phospholipase C beta; D043802:GTP-Binding Protein alpha Subunits, Gq-G11