Bou Sleiman Maroun S, Osman Dani, Massouras Andreas, Hoffmann Ary A, Lemaitre Bruno, Deplancke Bart
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.
Global Health Institute, School of Life Sciences, Station 19, EPFL, 1015 Lausanne, Switzerland.
Nat Commun. 2015 Jul 27;6:7829. doi: 10.1038/ncomms8829.
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.
肠道免疫能力涉及免疫、应激和再生过程。为了研究个体间肠道免疫能力差异的潜在决定因素，我们用昆虫病原细菌嗜虫假单胞菌对140个果蝇品系进行肠道感染，并观察到存活率存在广泛差异。通过全基因组关联分析，我们鉴定出了几种新的免疫调节因子。转录谱分析进一步表明，在感染前，抗性品系和易感品系之间的肠道分子状态就有所不同，其中一个涉及与活性氧（ROS）代谢相关基因的转录模块导致了这种差异。这种遗传和分子变异在生理上表现为，与易感品系相比，抗性品系的ROS活性较低、对ROS诱导剂的敏感性较低、病原体清除速度较快以及干细胞活性较高。这项研究为群体水平肠道免疫能力差异的潜在决定因素提供了新的见解，揭示了相对微小但系统的遗传和转录变异如何介导决定肠道感染易感性的明显生理差异。
