PT - JOURNAL ARTICLE AU - Seth M. Barribeau AU - Paul Schmid-Hempel AU - Ben M. Sadd TI - Royal decree: gene expression in transgenerationally immune primed bumblebee workers mimics a primary immune response AID - 10.1101/043638 DP - 2016 Jan 01 TA - bioRxiv PG - 043638 4099 - http://biorxiv.org/content/early/2016/03/15/043638.short 4100 - http://biorxiv.org/content/early/2016/03/15/043638.full AB - Invertebrates lack the cellular and physiological machinery of the adaptive immune system, but show specificity in their immune response [1, 2] and immune priming [3-11]. Functionally, immune priming is comparable to immune memory in vertebrates. Individuals that have survived exposure to a given parasite are better protected against subsequent exposures. Protection may be cross-reactive (e.g. [12]), but demonstrations of persistent and specific protection in invertebrates are increasing [3, 5]. This immune priming can cross generations ("trans-generational" immune priming) [4, 8], preparing offspring for the prevailing parasite environment. While these phenomena gain increasing support, the mechanistic foundations underlying such immune priming, both within and across generations, remain largely unknown. Using a transcriptomic approach, we show a bacterial challenge to bumblebee queens, known to induce trans-generational immune priming, alters daughter (worker) gene expression. Daughters, even when unchallenged themselves, constitutively express a core set of the genes induced upon direct bacterial exposure, including high expression of antimicrobial peptides, a beta-glucan receptor protein implicated in bacterial recognition and the induction of the toll signaling pathway[13], and slit-3 which is important in honeybee immunity[14]. Maternal challenge results in a distinct upregulation of their daughters’ immune system, with a signature overlapping with the induced individual response to a direct immune challenge. This will mediate mother-offspring protection, but also associated costs related to reconfiguration of constitutive immune expression. Identification of conserved immune pathways in memory-like responses has important implications for our understanding of the innate immune system, including the innate components in vertebrates, which share many of these pathways[15].Author Summary Invertebrate individuals surviving exposure to an infectious disease can become better at fighting future infection by that same disease. This protection, known as immune priming, can even be transferred to the individuals’ offspring. The functional outcome is very similar to that of vertebrate immune memory, but the mechanisms of how invertebrates achieve immune priming within an individual or across generations remain enigmatic. We found that bumblebee daughters of mothers exposed to a simulated bacterial infection express strongly many of the genes that they would activate if they were themselves infected. Our results show how immune priming across generations might be produced in bumblebees. Many parts of the invertebrate immune system are shared with us, and thus our study also sheds a light on how diverse immune memory-like effects could be achieved.