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Schneider, D.S. & Ayres, J.S. Two ways to survive infection: what resistance and tolerance can teach us about treating infectious diseases. Nat. Rev. Immunol. 8, 889-895

Department of Microbiology and Immunology, Stanford University, Stanford, California 94305, USA.
Nature Reviews Immunology (Impact Factor: 34.99). 11/2008; 8(11):889-95. DOI: 10.1038/nri2432
Source: PubMed

ABSTRACT

A host can evolve two types of defence mechanism to increase its fitness when challenged with a pathogen: resistance and tolerance. Immunology is a well-defined field in which the mechanisms behind resistance to infection are dissected. By contrast, the mechanisms behind the ability to tolerate infections are studied in a less methodical manner. In this Opinion, we provide evidence that animals have specific tolerance mechanisms and discuss their potential clinical impact. It is important to distinguish between these two defence mechanisms because they have different pathological and epidemiological effects. An increased understanding of tolerance to pathogen infection could lead to more efficient treatments for infectious diseases and a better description of host-pathogen interactions.

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Available from: David Schneider, Jun 28, 2015
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    • "CBA mice should probably also be considered tolerant to the infection. Tolerance is a concept routinely used by phytopathologists that has been recently adapted to animal infections (Raberg et al., 2007) and refers to individuals that withstand the infection, paying small or no costs at all (Schneider and Ayres, 2008). Even though immunological tolerance and tolerance of the infection are not strictly synonymous terms, tolerance of the infection often involves the activation of immunological effectors that prevent immunopathology (Medzhitov et al., 2012). "
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    ABSTRACT: The outcome of the encounter between a host and a parasite depends on the synergistic effects of the genetics of the two partners and the environment (sensulato) where the interaction takes place. Reaction norms can depict how host and parasite traits vary across environmental ranges for different genotypes. Here, we performed a large scale experiment where three strains of laboratory mice (SJL, BALB/c and CBA) were infected with four doses of the intestinal nematode Heligmosomoides polygyrus. An increasing infective dose can be considered as a proxy for the environment-dependent risk incontracting the infection. We looked at the fitness traits of hosts and parasites, and assessed the underlying immunological functions likely to affect the observed pattern of resistance/susceptibility/tolerance. We found that the infective dose had a strong effect on both host fitness and parasite performance. Interestingly, for most traits, host genotypes did not rank consistently across the increasing infective doses and according to the expected pattern of strain-specific resistance/susceptibility/tolerance. Analyses of cytokine production allowed better understanding of the mechanistic basis underlying variations in fitness-linked traits. The infective dose affected the shape of the reaction norms of the cytokines IL-4, IL-10 and IL-6. Dose-dependent variation in cytokine production explained, moreover, the strain-specific pattern of infection cost, host resistance and parasite performance. As long as the infective dose increased, there was a marked shift towards a pro-inflammatory status in the SJL strain of mice that was positively correlated with cost of the infection and parasite performance. Overall, our study strongly suggests that the notion of host resistance is labile and depends on the environmental conditions where the interaction takes place. Moreover, integrating information on fitness-linked traits and the underlying mechanisms seems essential for a better understanding of host and parasite adaptations across variable environments.
    Preview · Article · Nov 2015 · International journal for parasitology
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    • "More recently, approaches that target the damage done by parasites, without directly targeting the parasite itself, have been explored as alternatives (Vale et al. 2014). This distinction is akin to the distinction between resistance and tolerance mechanisms in the eco-immunology literature (Schneider and Ayres, 2008). It is important to understand how vaccines with different modes of action drive virulence evolution. "
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    ABSTRACT: Why is it that some parasites cause high levels of host damage (i.e. virulence) whereas others are relatively benign? There are now numerous reviews of virulence evolution in the literature but it is nevertheless still difficult to find a comprehensive treatment of the theory and data on the subject that is easily accessible to non-specialists. Here we attempt to do so by distilling the vast theoretical literature on the topic into a set of relatively few robust predictions. We then provide a comprehensive assessment of the available empirical literature that tests these predictions. Our results show that there have been some notable successes in integrating theory and data but also that theory and empiricism in this field do not ‘speak’ to each other very well. We offer a few suggestions for how the connection between the two might be improved.
    Full-text · Article · Aug 2015 · Parasitology
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    • "One reason may be that other aspects of senescence make older animals more vulnerable to infection. For instance, the ability to tolerate bacterial infection decreases with age (Ayres & Schneider 2008). Old individuals may thus rely on active resistance to bacterial infection, leading to selection for ever-increasing immune function with age. "
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    ABSTRACT: 1.In most animals, ageing is associated with a decline in immune function (immune senescence). However, different components of the immune system seem to age differentially, and many studies do not measure the ultimate fitness consequences of immune function after infection. Previous work shows that immune function may be traded off with other fitness components such as reproduction. It is possible that age alters the nature of these trade-offs, particularly in conjunction with factors such as gender and mating that can also affect investment in immune function. 2.We tested the impact of age, sex and mating on post-infection survivorship in Tribolium castaneum flour beetles, as well as the components of baseline constitutive innate immunity and external (secreted) immune function in uninfected individuals. We also tested whether the reproductive ability of uninfected females is traded off with immune function (baseline innate and external immunity) and post-infection survivorship across age groups. 3.We found that age, sex and mating significantly affected immune components and infection outcome, although the magnitude and nature of the impact varied in each case. We found that older beetles were more susceptible to infection by the pathogen Bacillus thuringiensis even though major components of the constitutive innate immune defence (antibacterial and phenoloxidase activity) remained unchanged or improved with age. Thus, these aspects of innate immunity cannot explain the observed decline in post-infection survival of older beetles. We did not find trade-offs between the reproductive ability of uninfected females and their immune function. In contrast to innate immunity, external immunity showed an overall decline with age but was also affected by sex and mating. Finally, we show that bacterial infection alters external immunity via complex interactions between age, sex and mating status. 4.Our work uncovers novel interactions between age, sex and mating that can determine the evolution and outcome of immunosenescence by affecting the time course of relative investment in different immune and fitness components. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · Aug 2015 · Journal of Animal Ecology
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