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Genetic, molecular and physiological basis of variation in Drosophila gut immunocompetence.

Bou Sleiman MS, Osman D, Massouras A, Hoffmann AA, Lemaitre B, Deplancke B - Nat Commun (2015)

Bottom Line: Gut immunocompetence involves immune, stress and regenerative processes.Using genome-wide association analysis, we identify several novel immune modulators.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Diversity in ROS metabolism is a feature of variable susceptibility.(a–b) Measurement of ROS activity in flies before and after Pseudomonas entomophila infection reveals lower ROS levels in resistant compared with susceptible DGRP lines (mean normalized absorbance ± s.d., n=5 females per line and replicate, three replicates, ANOVA P<0.0001 for difference between susceptibility classes in both conditions). The dashed line marks the maximum level in resistant lines. (c) Percentage of dead female flies 3 days after Paraquat treatment. Percentages are averages from three experiments (± s.d., n>60 females/line, ANOVA P<0.0001 for difference between susceptibility classes).
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f5: Diversity in ROS metabolism is a feature of variable susceptibility.(a–b) Measurement of ROS activity in flies before and after Pseudomonas entomophila infection reveals lower ROS levels in resistant compared with susceptible DGRP lines (mean normalized absorbance ± s.d., n=5 females per line and replicate, three replicates, ANOVA P<0.0001 for difference between susceptibility classes in both conditions). The dashed line marks the maximum level in resistant lines. (c) Percentage of dead female flies 3 days after Paraquat treatment. Percentages are averages from three experiments (± s.d., n>60 females/line, ANOVA P<0.0001 for difference between susceptibility classes).

Mentions: To investigate the physiological relevance of ROS in mediating inter-individual differences in gut immunocompetence, we compared ROS levels in resistant versus susceptible lines (Fig. 5a,b). Importantly, ROS levels were significantly lower in resistant lines in both conditions (ANOVA P=2.98 × 10−7 for susceptibility class in unchallenged condition and P=1.43 × 10−11 in challenged condition). This may reflect a more efficient ROS metabolism in resistant lines, possibly mediated by the higher expression levels of the majority of genes in the focal module #96 compared with susceptible lines (Fig. 4f). Since too much ROS inhibits translation and epithelial renewal resulting in lethality31, it appears that resistant lines utilize ROS in a more effective and less noxious manner than susceptible lines (Fig. 1c,e). To investigate this hypothesis, we evaluated the survival of the same lines to ingestion of paraquat, a ROS-catalyzing chemical reagent. Most susceptible lines showed higher lethality compared with resistant lines (Fig. 5c), supporting the role of ROS as one of the principal components underlying variation in gut immunocompetence.


Genetic, molecular and physiological basis of variation in Drosophila gut immunocompetence.

Bou Sleiman MS, Osman D, Massouras A, Hoffmann AA, Lemaitre B, Deplancke B - Nat Commun (2015)

Diversity in ROS metabolism is a feature of variable susceptibility.(a–b) Measurement of ROS activity in flies before and after Pseudomonas entomophila infection reveals lower ROS levels in resistant compared with susceptible DGRP lines (mean normalized absorbance ± s.d., n=5 females per line and replicate, three replicates, ANOVA P<0.0001 for difference between susceptibility classes in both conditions). The dashed line marks the maximum level in resistant lines. (c) Percentage of dead female flies 3 days after Paraquat treatment. Percentages are averages from three experiments (± s.d., n>60 females/line, ANOVA P<0.0001 for difference between susceptibility classes).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4525169&req=5

f5: Diversity in ROS metabolism is a feature of variable susceptibility.(a–b) Measurement of ROS activity in flies before and after Pseudomonas entomophila infection reveals lower ROS levels in resistant compared with susceptible DGRP lines (mean normalized absorbance ± s.d., n=5 females per line and replicate, three replicates, ANOVA P<0.0001 for difference between susceptibility classes in both conditions). The dashed line marks the maximum level in resistant lines. (c) Percentage of dead female flies 3 days after Paraquat treatment. Percentages are averages from three experiments (± s.d., n>60 females/line, ANOVA P<0.0001 for difference between susceptibility classes).
Mentions: To investigate the physiological relevance of ROS in mediating inter-individual differences in gut immunocompetence, we compared ROS levels in resistant versus susceptible lines (Fig. 5a,b). Importantly, ROS levels were significantly lower in resistant lines in both conditions (ANOVA P=2.98 × 10−7 for susceptibility class in unchallenged condition and P=1.43 × 10−11 in challenged condition). This may reflect a more efficient ROS metabolism in resistant lines, possibly mediated by the higher expression levels of the majority of genes in the focal module #96 compared with susceptible lines (Fig. 4f). Since too much ROS inhibits translation and epithelial renewal resulting in lethality31, it appears that resistant lines utilize ROS in a more effective and less noxious manner than susceptible lines (Fig. 1c,e). To investigate this hypothesis, we evaluated the survival of the same lines to ingestion of paraquat, a ROS-catalyzing chemical reagent. Most susceptible lines showed higher lethality compared with resistant lines (Fig. 5c), supporting the role of ROS as one of the principal components underlying variation in gut immunocompetence.

Bottom Line: Gut immunocompetence involves immune, stress and regenerative processes.Using genome-wide association analysis, we identify several novel immune modulators.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus