000212233 001__ 212233
000212233 005__ 20190416220325.0
000212233 0247_ $$2doi$$a10.1038/ncomms8829
000212233 022__ $$a2041-1723
000212233 02470 $$2ISI$$a000358860900009
000212233 037__ $$aARTICLE
000212233 245__ $$aGenetic, molecular and physiological basis of variation in Drosophila gut immunocompetence
000212233 269__ $$a2015
000212233 260__ $$aLondon$$bNature Publishing Group$$c2015
000212233 300__ $$a10
000212233 336__ $$aJournal Articles
000212233 520__ $$aGut immunocompetence involves immune, stress and regenerative processes. To investigate the determinants underlying inter-individual variation in gut immunocompetence, we perform enteric infection of 140 Drosophila lines with the entomopathogenic bacterium Pseudomonas entomophila and observe extensive variation in survival. Using genome-wide association analysis, we identify several novel immune modulators. Transcriptional profiling further shows that the intestinal molecular state differs between resistant and susceptible lines, already before infection, with one transcriptional module involving genes linked to reactive oxygen species (ROS) metabolism contributing to this difference. This genetic and molecular variation is physiologically manifested in lower ROS activity, lower susceptibility to ROS-inducing agent, faster pathogen clearance and higher stem cell activity in resistant versus susceptible lines. This study provides novel insights into the determinants underlying population-level variability in gut immunocompetence, revealing how relatively minor, but systematic genetic and transcriptional variation can mediate overt physiological differences that determine enteric infection susceptibility.
000212233 700__ $$aSleiman, Maroun S. Bou$$uEcole Polytech Fed Lausanne, Global Hlth Inst, Sch Life Sci, Stn 19, CH-1015 Lausanne, Switzerland
000212233 700__ $$0244390$$aOsman, Dani$$g201327$$uEcole Polytech Fed Lausanne, Global Hlth Inst, Sch Life Sci, Stn 19, CH-1015 Lausanne, Switzerland
000212233 700__ $$0244792$$aMassouras, Andreas$$g192097$$uEcole Polytech Fed Lausanne, Inst Bioengn, Sch Life Sci, Stn 19, CH-1015 Lausanne, Switzerland
000212233 700__ $$aHoffmann, Ary A.$$uUniv Melbourne, Sch BioSci, Inst Bio21, Parkville, Vic 3010, Australia
000212233 700__ $$0244384$$aLemaitre, Bruno$$g178546$$uEcole Polytech Fed Lausanne, Global Hlth Inst, Sch Life Sci, Stn 19, CH-1015 Lausanne, Switzerland
000212233 700__ $$0244717$$aDeplancke, Bart$$g182376$$uEcole Polytech Fed Lausanne, Inst Bioengn, Sch Life Sci, Stn 19, CH-1015 Lausanne, Switzerland
000212233 773__ $$j6$$q7829$$tNature Communications
000212233 8564_ $$s1144071$$uhttps://infoscience.epfl.ch/record/212233/files/ncomms8829.pdf$$yPublisher's version$$zPublisher's version
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000212233 937__ $$aEPFL-ARTICLE-212233
000212233 973__ $$aEPFL$$rREVIEWED$$sPUBLISHED
000212233 980__ $$aARTICLE