ABSTRACT
A trade-off hypothesis pertains to the biased allocation of limited resources between two of the most important fitness traits, reproduction and survival to infection. This quid pro quo manifests itself within animals prioritizing their energetic needs according to genetic circuits balancing metabolism, germline activity and immune response. Key evidence supporting this hypothesis includes dipteran fecundity being compromised by systemic immunity, and female systemic immunity being compromised by mating. Here, we reveal a local trade-off taking place in the female Drosophila midgut upon immune challenge. Genetic manipulation of intestinal motility, permeability, regeneration and three key midgut immune pathways provides evidence of an antagonism between specific aspects of intestinal defense and fecundity. That is, juvenile hormone (JH)-controlled egg laying, lipid droplet utilization and insulin receptor expression are specifically compromised by the immune deficiency (Imd) and the dual oxidase (Duox) signaling in the midgut epithelium. Moreover, antimicrobial peptide (AMP) expression under the control of the Imd pathway is inhibited upon mating and JH signaling in the midgut. Local JH signaling is further implicated in midgut dysplasia, inducing stem cell-like clusters and gut permeability. Thus, midgut JH signaling compromises host defense to infection by reducing Imd-controlled AMP expression and by inducing dysplasia, while midgut signaling through the Imd and Duox pathways compromises JH-guided metabolism and fecundity.
ABSTRACT
Physiology, fitness and disease phenotypes are complex traits exhibiting continuous variation in natural populations. To understand complex trait gene functions transgenic lines of undefined genetic background are often combined to assess quantitative phenotypes ignoring the impact of genetic polymorphisms. Here, we used inbred wild-type strains of the Drosophila Genetics Reference Panel to assess the phenotypic variation of six physiological and fitness traits, namely, female fecundity, survival and intestinal mitosis upon oral infection, defecation rate and fecal pH upon oral infection, and terminal tracheal cell branching in hypoxia. We found continuous variation in the approximately 150 strains tested for each trait, with extreme values differing by more than four standard deviations for all traits. In addition, we assessed the effects of commonly used Drosophila UAS-RNAi transgenic strains and their backcrossed isogenized counterparts, in the same traits plus baseline intestinal mitosis and tracheal branching in normoxia, in heterozygous conditions, when only half of the genetic background was different among strains. We tested 20 non-isogenic strains (10 KK and 10 GD) from the Vienna Drosophila Resource Center and their isogenized counterparts without Gal4 induction. Survival upon infection and female fecundity exhibited differences in 50% and 40% of the tested isogenic vs. non-isogenic pairs, respectively, whereas all other traits were affected in only 10-25% of the cases. When 11 isogenic and their corresponding non-isogenic UAS-RNAi lines were expressed ubiquitously with Gal4, 4 isogenic vs. non-isogenic pairs exhibited differences in survival to infection. Furthermore, when a single UAS-RNAi line was crossed with the same Gal4 transgene inserted in different genetic backgrounds, the quantitative variations observed were unpredictable on the basis of pure line performance. Thus, irrespective of the trait of interest, the genetic background of commonly used transgenic strains needs to be considered carefully during experimentation.
