title: Coevolutionary feedback elevates constitutive immune defence: a protein network model.
abstract: BACKGROUND
  Organisms have evolved a variety of defence mechanisms against natural enemies, which are typically used at the expense of other life history components. Induced defence mechanisms impose minor costs when pathogens are absent, but mounting an induced response can be time-consuming. Therefore, to ensure timely protection, organisms may partly rely on constitutive defence despite its sustained cost that renders it less economical. Existing theoretical models addressing the optimal combination of constitutive versus induced defence focus solely on host adaptation and ignore the fact that the efficacy of protection depends on genotype-specific host-parasite interactions. Here, we develop a signal-transduction network model inspired by the invertebrate innate immune system, in order to address the effect of parasite coevolution on the optimal combination of constitutive and induced defence.
  
  
  RESULTS
  Our analysis reveals that coevolution of parasites with specific immune components shifts the host's optimal allocation from induced towards constitutive immunity. This effect is dependent upon whether receptors (for detection) or effectors (for elimination) are subjected to parasite counter-evolution. A parasite population subjected to a specific immune receptor can evolve heightened genetic diversity, which makes parasite detection more difficult for the hosts. We show that this coevolutionary feedback renders the induced immune response less efficient, forcing the hosts to invest more heavily in constitutive immunity. Parasites diversify to escape elimination by a specific effector too. However, this diversification does not alter the optimal balance between constitutive and induced defence: the reliance on constitutive defence is promoted by the receptor's inability to detect, but not the effectors' inability to eliminate parasites. If effectors are useless, hosts simply adapt to tolerate, rather than to invest in any defence against parasites. These contrasting results indicate that evolutionary feedback between host and parasite populations is a key factor shaping the selection regime for immune networks facing antagonistic coevolution.
  
  
  CONCLUSIONS
  Parasite coevolution against specific immune defence alters the prediction of the optimal use of defence, and the effect of parasite coevolution varies between different immune components.
authors.affiliation: Groningen Institute for Evolutionary Life Sciences, University of Groningen, P.O. Box 11103, CC Groningen, 9700, The Netherlands. tsukushi.kamiya@mail.utoronto.ca.|Department of Ecology and Evolutionary Biology, University of Toronto, 25 Willcocks Street, Toronto, Canada. tsukushi.kamiya@mail.utoronto.ca.
authors.forename: Tsukushi
authors.initials: T
authors.lastname: Kamiya
authors.affiliation: Groningen Institute for Evolutionary Life Sciences, University of Groningen, P.O. Box 11103, CC Groningen, 9700, The Netherlands.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Oña
authors.affiliation: Groningen Institute for Evolutionary Life Sciences, University of Groningen, P.O. Box 11103, CC Groningen, 9700, The Netherlands.
authors.forename: Bregje
authors.initials: B
authors.lastname: Wertheim
authors.affiliation: Groningen Institute for Evolutionary Life Sciences, University of Groningen, P.O. Box 11103, CC Groningen, 9700, The Netherlands.
authors.forename: G Sander
authors.initials: GS
authors.lastname: van Doorn
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D056704:Adaptive Immunity; D000818:Animals; D019143:Evolution, Molecular; D014644:Genetic Variation; D006790:Host-Parasite Interactions; D007113:Immunity, Innate; D056747:Immunomodulation; D008954:Models, Biological; D010271:Parasites / Q000235:genetics / Q000276:immunology*; D010272:Parasitic Diseases / Q000235:genetics / Q000276:immunology* / Q000469:parasitology; D060066:Protein Interaction Maps; D015398:Signal Transduction
keywords: Constitutive immunity; Host-parasite coevolution; Immune network evolution; Individual-based simulation; Induced immunity; Optimal defence