Microbiome remodeling influences Drosophila immune response across generations
Authors: Krystal Maya-Maldonado; Nichole A. Broderick
Affiliation: Johns Hopkins University
Keywords: k. host/pathogen interactions; k. host/pathogen interactions
In insects, including Drosophila melanogaster, the microbiome can exert intergenerational effects on host physiological processes through impacts on reproduction and development. In addition, specific microbiota members have been shown to influence mating, reproductive behavior, and development across generations.
Relatedly, previous studies in Drosophila and other insects have shown that immune status can be transmitted to progeny, a process referred to as transgenerational immunity. While several mechanisms of transgenerational immunity have been proposed, these have focused mainly on the transfer of an immunological experience to the offspring. Immune status is also known to be influenced by the microbiome, but the role of microbiota in transgenerational immunity has not been as well studied.
To address this knowledge gap, here we examined how interactions between a host, its’ microbiome, and gut pathogen (s) modulate host immunity and microbiome composition across generations. First, we analyzed how the parental microbiome influences outcome in offspring immunity. We used the well-standardized protocols in the Drosophila model to get germ-free flies (axenic (AX) flies), and we compared them with conventional reared (CR) flies, which contain a native microbiota. Parents from each condition (CR or AX) were challenged orally with Pseudomonas entomophila, and the offspring were reared to the next generation. In the offspring, females were challenged with P. entomophila orally and we recorded survival, pathogen bacterial load, microbiome composition, and gene expression to analyze how the offspring respond to the challenge. This strategy was applied across two generations (offspring adults in F1, and F2). We found that P. entomophila persist in food where F1 develops, causing changes in microbiome composition of both the food and in the offspring. Interestingly, when we challenge F1 adults with P. entomophila we observed a better survival in the offspring from parents that were challenged, although pathogen bacterial load is the same between the offspring from parents’ challenge and unchallenged. Our results suggest an immune tolerance effect is mediated by microbiome alterations across generations. Future studies will further characterize this mechanism of tolerance, as well as examine whether there have been genetic or transcriptional changes in the microbiome or pathogen.