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      The Immunology of Wild Rodents: Current Status and Future Prospects

      review-article
      1 , * , 2
      Frontiers in Immunology
      Frontiers Media S.A.
      mouse, rat, vole, rodent, immune, immunology, wild

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          Abstract

          Wild animals’ immune responses contribute to their evolutionary fitness. These responses are moulded by selection to be appropriate to the actual antigenic environment in which the animals live, but without imposing an excessive energetic demand which compromises other component of fitness. But, exactly what these responses are, and how they compare with those of laboratory animals, has been little studied. Here, we review the very small number of published studies of immune responses of wild rodents, finding general agreement that their humoral (antibody) responses are highly elevated when compared with those of laboratory animals, and that wild rodents’ cellular immune system reveals extensive antigenic exposure. In contrast, proliferative and cytokine responses of ex vivo-stimulated immune cells of wild rodents are typically depressed compared with those of laboratory animals. Collectively, these responses are appropriate to wild animals’ lives, because the elevated responses reflect the cumulative exposure to infection, while the depressed proliferative and cytokine responses are indicative of effective immune homeostasis that minimizes immunopathology. A more comprehensive understanding of the immune ecology of wild animals requires (i) understanding the antigenic load to which wild animals are exposed, and identification of any key antigens that mould the immune repertoire, (ii) identifying immunoregulatory processes of wild animals and the events that induce them, and (iii) understanding the actual resource state of wild animals, and the immunological consequences that flow from this. Together, by extending studies of wild rodents, particularly addressing these questions (while drawing on our immunological understanding of laboratory animals), we will be better able to understand how rodents’ immune responses contribute to their fitness in the wild.

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          Most cited references43

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          Recapitulating adult human immune traits in laboratory mice by normalizing environment

          Our current understanding of immunology was largely defined in laboratory mice because of experimental advantages including inbred homogeneity, tools for genetic manipulation, the ability to perform kinetic tissue analyses starting with the onset of disease, and tractable models. Comparably reductionist experiments are neither technically nor ethically possible in humans. Despite revealing many fundamental principals of immunology, there is growing concern that mice fail to capture relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside 1–8 . Laboratory mice live in abnormally hygienic “specific pathogen free” (SPF) barrier facilities. Here we show that the standard practice of laboratory mouse husbandry has profound effects on the immune system and that environmental changes result in better recapitulation of features of adult humans. Laboratory mice lack effector-differentiated and mucosally distributed memory T cells, which more closely resembles neonatal than adult humans. These cell populations were present in free-living barn populations of feral mice, pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting a role for environment. Consequences of altering mouse housing profoundly impacted the cellular composition of the innate and adaptive immune system and resulted in global changes in blood cell gene expression patterns that more closely aligned with immune signatures of adult humans rather than neonates, altered the mouse’s resistance to infection, and impacted T cell differentiation to a de novo viral infection. These data highlight the impact of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modeling immunological events in free-living organisms, including humans.
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            The comparative immunology of wild and laboratory mice, Mus musculus domesticus

            The laboratory mouse is the workhorse of immunology, used as a model of mammalian immune function, but how well immune responses of laboratory mice reflect those of free-living animals is unknown. Here we comprehensively characterize serological, cellular and functional immune parameters of wild mice and compare them with laboratory mice, finding that wild mouse cellular immune systems are, comparatively, in a highly activated (primed) state. Associations between immune parameters and infection suggest that high level pathogen exposure drives this activation. Moreover, wild mice have a population of highly activated myeloid cells not present in laboratory mice. By contrast, in vitro cytokine responses to pathogen-associated ligands are generally lower in cells from wild mice, probably reflecting the importance of maintaining immune homeostasis in the face of intense antigenic challenge in the wild. These data provide a comprehensive basis for validating (or not) laboratory mice as a useful and relevant immunological model system.
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              Optimal immune responses: immunocompetence revisited.

              The function of the immune system of an animal is to provide defence against infection, in order to maximize fitness. Understanding this and, particularly, how limiting resources are traded off between costly immune responses and other physiological demands, is central to properly understanding life-history traits and their evolution. Here, we propose that functional (rather than immunological) measures of immune responses should be used when investigating this. We further suggest that optimal immune responses are context specific, rather than generic; that is, a maximum immune response is not necessarily optimal. The nature of an optimal immune response will depend on the specific circumstances and infection status of the animal. Identifying and understanding such optimality requires that the effects of different immune strategies on fitness be considered.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                14 November 2017
                2017
                : 8
                : 1481
                Affiliations
                [1] 1School of Biological Sciences, University of Bristol , Bristol, United Kingdom
                [2] 2Department of Immunology and Infection, London School of Hygiene and Tropical Medicine , London, United Kingdom
                Author notes

                Edited by: Andrew Steven Flies, University of Tasmania, Australia

                Reviewed by: Beatriz Novoa, Consejo Superior de Investigaciones Científicas (CSIC), Spain; Joachim Kurtz, Universität Münster, Germany; Stephen Christopher Jameson, University of Minnesota, United States

                *Correspondence: Mark Viney, mark.viney@ 123456bristol.ac.uk

                Present address: Eleanor M. Riley, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian EH25 9RG, United Kingdom

                Specialty section: This article was submitted to Comparative Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2017.01481
                5694458
                cf28f341-275a-4bbf-b87e-9b0be4c30d5d
                Copyright © 2017 Viney and Riley.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 30 August 2017
                : 23 October 2017
                Page count
                Figures: 0, Tables: 1, Equations: 0, References: 45, Pages: 9, Words: 7952
                Categories
                Immunology
                Review

                Immunology
                mouse,rat,vole,rodent,immune,immunology,wild
                Immunology
                mouse, rat, vole, rodent, immune, immunology, wild

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