title: Genetic, molecular and physiological basis of variation in Drosophila gut immunocompetence.
abstract: Gut 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.
authors.affiliation: 1] Global Health Institute, School of Life Sciences, Station 19, EPFL, 1015 Lausanne, Switzerland [2] Institute of Bioengineering, School of Life Sciences, Station 19, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Maroun S
authors.initials: MS
authors.lastname: Bou Sleiman
authors.affiliation: Global Health Institute, School of Life Sciences, Station 19, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Dani
authors.initials: D
authors.lastname: Osman
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Station 19, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Massouras
authors.affiliation: School of BioSciences, Bio21 Institute, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Ary A
authors.initials: AA
authors.lastname: Hoffmann
authors.affiliation: Global Health Institute, School of Life Sciences, Station 19, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lemaitre
authors.affiliation: 1] Institute of Bioengineering, School of Life Sciences, Station 19, EPFL, 1015 Lausanne, Switzerland [2] Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
authors.forename: Bart
authors.initials: B
authors.lastname: Deplancke
mesh_terms: D000818:Animals; D058491:Bacterial Load; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D007121:Immunocompetence / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D011549:Pseudomonas / Q000276:immunology; D011552:Pseudomonas Infections / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D017382:Reactive Oxygen Species / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D017423:Sequence Analysis, RNA
chemical_list: D029721:Drosophila Proteins; D017382:Reactive Oxygen Species