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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

Gut immunocompetence is a largely additive, complex trait.(a) The genomic relationship matrix shows an absence of genetic relatedness among either resistant or susceptible lines respectively. (b) Percentage death for F1 flies in a full diallel cross between four susceptible and four resistant DGRP lines (by 3 days post-enteric infection with Pseudomonas entomophila (A 100)).
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f2: Gut immunocompetence is a largely additive, complex trait.(a) The genomic relationship matrix shows an absence of genetic relatedness among either resistant or susceptible lines respectively. (b) Percentage death for F1 flies in a full diallel cross between four susceptible and four resistant DGRP lines (by 3 days post-enteric infection with Pseudomonas entomophila (A 100)).

Mentions: It is conceivable that physiological and survival differences between resistant and susceptible lines are a mere consequence of high genetic relatedness among lines from each phenotypic class. To explore this possibility, we used the available genetic relationship matrix for the eight DGRP lines (http://dgrp2.gnets.ncsu.edu/), but did not observe genetic clustering of phenotypic classes, as expected18 (Fig. 2a). However, a significant part of the observed variation in survival is due to genetic factors as the heritable component estimate is 0.61 (Methods). To gain insights into the genetic architecture of survival, we performed a complete diallel cross, where we generated all possible hybrid combinations by crossing the eight lines to each other. We then measured their susceptibility to P. entomophila infection. The F1 progeny from crosses between different resistant lines were resistant (Fig. 2b) and the F1 progeny from crosses between different susceptible lines were mainly susceptible, thus there was no evidence of consistent heterosis. The lack of resistance appearing in crosses between susceptible lines implies that susceptibility is not a mere consequence of inbreeding depression. Moreover, F1 progeny from crosses between resistant and susceptible lines tended to exhibit an intermediate susceptibility phenotype as expected when there are additive effects. Indeed, an analysis of the diallel cross data (Supplementary Table 2) revealed both additive effects reflected in general combining ability (ANOVA P=0.00001) and dominance effects reflected in specific combining ability (ANOVA P<0.00001)32. There were also various interactions between strains due to male and female parental combinations (Supplementary Table 2), suggesting that the extent of susceptibility depends on the specific combination of strains tested. In general, these patterns indicate that natural variation in survival to infection is partly additive, but also depends on the combination of strains being crossed, suggesting a complex genetic architecture.


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)

Gut immunocompetence is a largely additive, complex trait.(a) The genomic relationship matrix shows an absence of genetic relatedness among either resistant or susceptible lines respectively. (b) Percentage death for F1 flies in a full diallel cross between four susceptible and four resistant DGRP lines (by 3 days post-enteric infection with Pseudomonas entomophila (A 100)).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f2: Gut immunocompetence is a largely additive, complex trait.(a) The genomic relationship matrix shows an absence of genetic relatedness among either resistant or susceptible lines respectively. (b) Percentage death for F1 flies in a full diallel cross between four susceptible and four resistant DGRP lines (by 3 days post-enteric infection with Pseudomonas entomophila (A 100)).
Mentions: It is conceivable that physiological and survival differences between resistant and susceptible lines are a mere consequence of high genetic relatedness among lines from each phenotypic class. To explore this possibility, we used the available genetic relationship matrix for the eight DGRP lines (http://dgrp2.gnets.ncsu.edu/), but did not observe genetic clustering of phenotypic classes, as expected18 (Fig. 2a). However, a significant part of the observed variation in survival is due to genetic factors as the heritable component estimate is 0.61 (Methods). To gain insights into the genetic architecture of survival, we performed a complete diallel cross, where we generated all possible hybrid combinations by crossing the eight lines to each other. We then measured their susceptibility to P. entomophila infection. The F1 progeny from crosses between different resistant lines were resistant (Fig. 2b) and the F1 progeny from crosses between different susceptible lines were mainly susceptible, thus there was no evidence of consistent heterosis. The lack of resistance appearing in crosses between susceptible lines implies that susceptibility is not a mere consequence of inbreeding depression. Moreover, F1 progeny from crosses between resistant and susceptible lines tended to exhibit an intermediate susceptibility phenotype as expected when there are additive effects. Indeed, an analysis of the diallel cross data (Supplementary Table 2) revealed both additive effects reflected in general combining ability (ANOVA P=0.00001) and dominance effects reflected in specific combining ability (ANOVA P<0.00001)32. There were also various interactions between strains due to male and female parental combinations (Supplementary Table 2), suggesting that the extent of susceptibility depends on the specific combination of strains tested. In general, these patterns indicate that natural variation in survival to infection is partly additive, but also depends on the combination of strains being crossed, suggesting a complex genetic architecture.

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