251A Poster - 02. Immunity and the microbiome
Thursday April 07, 2:00 PM - 4:00 PM

Authors:
Scott Keith ^1,2; Brian Lazzaro ^1,2; Brooke McCartney ³

Affiliations:
1) Department of Entomology, Cornell University, Ithaca, NY; 2) Cornell Institute of Host-Microbe Interactions and Disease, Cornell University, Ithaca, NY; 3) Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA

Keywords:
k. host/pathogen interactions; e. endocrine function

Animals are continuously exposed to diverse populations of environmental microbes ranging from beneficial bacteria to harmful pathogens and must rapidly adjust energy metabolism and immune reactions in response. Circulating hormones can modulate the balance between interrelated physiological processes through effects on gene expression and cell biology. In Drosophila, ecdysone and insulin signaling sustain metabolic homeostasis, developmental growth, and immunity in the context of both commensal microbiota association and infection with pathogens. However we know little about the mechanisms of this regulation, including the extent to which these hormones facilitate immuno-metabolic crosstalk and how interactions with microbes shape that crosstalk. We have identified the neuronal synaptic plasticity factor Arc1, which is homologous to mammalian Arc/Arg3.1 proteins, as a novel host gene that supports larval metabolism and growth in response to microbiota perturbation. We found that Arc1 can function in the insulin-producing cells of the larval brain and the ecdysone-synthesizing prothoracic gland to support development in germ-free (GF) Drosophila, and that hallmarks of insulin and ecdysone signaling were perturbed in GF Arc1 mutants. We additionally discovered that flies lacking Arc1 exhibit altered antimicrobial peptide induction levels, increased microbial loads, and increased mortality after systemic infection with the bacterial pathogens Erwinia (Pectinobacter) carotovora and Providencia rettgeri. These data reveal an unexpected new role for Arc proteins, which have been previously studied exclusively in the context of the nervous system. Future work will test whether Arc1 regulation of ecdysone and insulin signaling affects immune responses to systemic infection. Ongoing research will directly investigate how the interplay between ecdysone and insulin signaling in the fat body regulates IMD pathway function and restructures energy metabolism to ensure survival of infection, potentially at the cost of resistance to other stressors like nutritional challenge. Through this work, we will better understand the mechanistic principles of hormone-mediated metabolic and immune system regulation in the context of host-microbe interactions.