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.

Immune response and gut microbial community structure in bumblebees after microbiota transplants

“…suggested before [11]. We also found differential gene expression patterns among susceptible and resistant colony phenotypes, comparable with recent studies in Drosophila [22,31]. The recipient effect on the immune response may indicate inherent differences between the two genetic host resistance backgrounds in their ability to impose selection on the establishing community.…”

“…Nevertheless, if hosts have the ability to influence the establishment of the microbiota via the host immune system, we expect to find variation in the immune response towards different classes of microorganisms (i.e. beneficial and non-beneficial), and among the hosts themselves [21,22], similar to the variation in gene expression that underlies the specificity of host-parasite interactions [17,23]. Additionally, in different environments (i.e.…”

Host and Bacterial Factors Control Susceptibility of Drosophila melanogaster to Coxiella burnetii Infection

“…This study suggested that the Eiger-mediated immune response aided in the clearance of extracellular pathogens; however, mortality from intracellular-pathogen challenge was unchanged or reduced in Eiger mutants. Drosophila has also been used to reveal virulence factors associated with Francisella tularensis pathogenesis (34), gut immunocompetence during Pseudomonas entomophila infection (41), and phagocytic activity during Mycobacterium marinum infection (32). Taking the data together, the use of Drosophila to investigate bacterial pathogenesis and host immune responses identifies key signaling mechanisms that may lead to the development of novel therapeutics designed to control infection in natural hosts.…”

Gene regulatory mechanisms underlying the intestinal innate immune response

“…Importantly, the use of Drosophila allows assessing the impact of different infection states (i.e. no, mild, or severe infection) on distinct, but constant genetic backgrounds through the use of inbred fly lines [56 ]. In addition, it is proving an ideal model to study the molecular and physiological role of the intestinal microbiota in post-embryonic development and homeostasis [57][58][59].…”