Seasonal immunoregulation in a naturally occurringvertebrate

Background: Fishes show seasonal patterns of immunity, but such phenomena are imperfectly understood invertebrates generally, even in humans and mice. As these seasonal patterns may link to infectious disease riskand individual condition, the nature of their control has real practical implications. Here we characterize seasonaldynamics in the expression of conserved vertebrate immunity genes in a naturally-occurring piscine model, thethree-spined stickleback. Results: We made genome-wide measurements (RNAseq) of whole-fish mRNA pools (n = 36) at the end of summerand winter in contrasting habitats (riverine and lacustrine) and focussed on common trends to filter habitat-specificfrom overarching temporal responses. We corroborated this analysis with targeted year-round whole-fish geneexpression (Q-PCR) studies in a different year (n = 478). We also considered seasonal tissue-specific expression (6tissues) (n = 15) at a third contrasting (euryhaline) locality by Q-PCR, further validating the generality of the patternsseen in whole fish analyses. Extremes of season were the dominant predictor of immune expression (compared tosex, ontogeny or habitat). Signatures of adaptive immunity were elevated in late summer. In contrast, late winterwas accompanied by signatures of innate immunity (including IL-1 signalling and non-classical complementactivity) and modulated toll-like receptor signalling. Negative regulators of T-cell activity were prominent amongstwinter-biased genes, suggesting that adaptive immunity is actively down-regulated during winter rather thanpassively tracking ambient temperature. Network analyses identified a small set of immune genes that might lieclose to a regulatory axis. These genes acted as hubs linking summer-biased adaptive pathways, winter-biasedinnate pathways and other organismal processes, including growth, metabolic dynamics and responses to stressand temperature. Seasonal change was most pronounced in the gill, which contains a considerable concentrationof T-cell activity in the stickleback. Conclusions: Our results suggest major and predictable seasonal re-adjustments of immunity. Further considerationshould be given to the effects of such responses in seasonally-occurring disease