Abstract
BackgroundThe central paradigm of ecological immunology postulates that selection acts on immunity as to minimize its cost/benefit ratio. Costs of immunity may arise because the energetic requirements of the immune response divert resources that are no longer available for other vital functions. In addition to these resource-based costs, mis-directed or over-reacting immune responses can be particularly harmful for the host. In spite of the potential importance of immunopathology, most studies dealing with the evolution of the immune response have neglected such non resource-based costs. To keep the immune response under control, hosts have evolved regulatory pathways that should be considered when studying the target of the selection pressures acting on immunity. Indeed, variation in regulation may strongly modulate the negative outcome of immune activation, with potentially important fitness consequences.Methodology/Principal FindingsHere, we experimentally assessed the survival costs of reduced immune regulation by inhibiting an anti-inflammatory cytokine (IL-10) with anti-IL-10 receptor antibodies (anti-IL-10R) in mice that were either exposed to a mild inflammation or kept as control. The experiment was performed on young (3 months) and old (15 months) individuals, as to further assess the age-dependent cost of suppressing immune regulation. IL-10 inhibition induced high mortality in old mice exposed to the mild inflammatory insult, whereas no mortality was observed in young mice. However, young mice experienced a transitory lost in body mass when injected with the anti-IL-10R antibodies, showing that the treatment was to a lesser extent also costly for young individuals.ConclusionsThese results suggest a major role of immune regulation that deserves attention when investigating the evolution of immunity, and indicate that the capacity to down-regulate the inflammatory response is crucial for late survival and longevity.
Highlights
Costs and benefits of the immune response have attracted considerable attention in the last years among evolutionary biologists [1–3 for reviews]
These results suggest a major role of immune regulation that deserves attention when investigating the evolution of immunity, and indicate that the capacity to down-regulate the inflammatory response is crucial for late survival and longevity
Old individuals treated with anti-IL-10R and with lipopolysaccharide solution (LPS) suffered a substantially higher mortality rate compared to the other three groups (Log-Rank, x23 = 17.15, P = 0.0007, Figure 1), with mortality of anti-IL-10R/LPS mice occurring at days 2 and 3
Summary
Costs and benefits of the immune response have attracted considerable attention in the last years among evolutionary biologists [1–3 for reviews]. Most ecological immunology studies have focused on such resource-based costs of immunity [4,5], and with a few exceptions [6,7,8,9], have neglected resource independent costs. This is surprising, given the potentially devastating costs of autoimmunity. Costs of immunity may arise because the energetic requirements of the immune response divert resources that are no longer available for other vital functions In addition to these resource-based costs, mis-directed or over-reacting immune responses can be harmful for the host. Variation in regulation may strongly modulate the negative outcome of immune activation, with potentially important fitness consequences
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