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Physiological Costs of Mounting Immune Responses in Drosophila melanogaster
The physiological responses of organisms to short-term environmental stress, such as infection, can have long-term consequences for fitness, particularly if responses are inappropriate or nutrient resources are limited. My research takes advantage of a well-characterized set of Drosophila melanogaster mitochondrial-nuclear genotypes to investigate the energetic costs and life-history consequences of infection, which involves activation of underlying molecular pathways and aspects of cellular energy metabolism. The mitochondrial-nuclear genotype (simw501);OreR has compromised energy metabolism resulting in increased development time and decreased female fecundity. My research also leveraged a genotype RelE20, which has a deletion in the relish transcription factor upstream of IMD signaling to ascertain the costs of mounting immune responses. I first tested the hypothesis that compromised energetic function results in a cellular starvation-like state that is sensed via the same signaling pathways used to sense environmental nutrients. Energetically compromised individuals were resistant to the effects of both rapamycin and dietary restriction, providing evidence that inefficient cellular energetics interferes with nutrient sensing via insulin signaling. I then tested the hypothesis that mounting immune responses requires significant energetic investment. I predicted that energetically compromised individuals would have lower survival of infection with Providencia rettgeri, a natural bacterial pathogen. Survival post-infection significantly was significantly lower in energetically compromised adults relative to controls, an effect that was magnified in females. Energetically compromised females that survived infection had decreased fecundity relative to their sham-infected sisters, indicative of a trade-off between immunity and fecundity that was not apparent in wild-type females. I then tested the hypothesis that the energetic costs of mounting immune responses may be met by dynamic changes in whole-organism metabolism. I found that metabolic rate increased during infection only in flies with compromised energy metabolism. I also measured bacterial load in these individuals to test whether individual differences in metabolic rate were correlated with bacterial load and found no trend. In summary, these experiments indicate that mounting immune responses is energetically costly and can generate life-history trade-offs under energetically stressful conditions.
Buchanan, Justin L, "Physiological Costs of Mounting Immune Responses in Drosophila melanogaster" (2019). ETD collection for University of Nebraska - Lincoln. AAI13862449.