Transcriptional Profiling of Immune Priming in Drosophila melanogaster
Authors: Kevin Cabrera 1,2; Duncan Hoard 1; Zeba Wunderlich 1,2
Affiliations: 1) University of California, Irvine; 2) Boston University
Keywords: c. innate immunity; d. transcriptional regulation
Studying the way organisms fight off infections is a universally useful endeavor: anything that is alive has the possibility of getting sick. The historical paradigm in immunology focused on the binary distinction between the innate and adaptive immune systems. Increasingly, this binary convention has been challenged by the observations primed innate immune responses in organisms with and without an adaptive immune system. This so-termed “immune priming” helps organisms more effectively fight off a second infection after survival of an initial infection. Despite the wide prevalence of immune priming across many clades from plants to insects to mammals, much of the mechanistic work on this phenomenon has focused on cell-based mammalian models and lacked transcriptional characterization in insects. Here, we use Drosophila melanogaster to create a powerful, in vivo model for studying epigenetic control of immune priming. By infecting flies with an insect-derived strain of the Gram-positive bacterium Enterococcus faecalis, we modeled infection response and quantified enhanced survival in immune primed cohorts. We also tracked bacterial load over time and found preliminary evidence showing that the enhanced survival in primed cohorts does not correlate with differences in bacterial load. Using RNA-seq,we have tracked transcriptomic changes associated with immune priming in the primary immune organs of D. melanogaster, the fat body and hemocytes. Using differential expression analysis, we classified families of genes that remain activated throughout experiment, more efficiently re-activate upon re-infection, or are qualitatively unique to a primed immune response. Delineating the relative contributions of each of these mechanisms not only reveals the drivers of infection survival, but also suggests epigenetic mechanisms of gene regulation and tradeoffs between the immune response and other biological processes. By integrating gene expression with chromatin remodeling events and the effect of gene deletion on priming ability, we begin shortlisting regulatory elements that may be driving primed immune response. In this way, we unveil a concerted mechanism explaining immune priming in the fly.