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


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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    • "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.
    Parasitology 08/2015; -1:1-16. DOI:10.1017/S003118201500092X · 2.56 Impact Factor
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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.
    Journal of Animal Ecology 08/2015; DOI:10.1111/1365-2656.12433 · 4.50 Impact Factor
    • "It seems in the light of our finding that an individual's susceptibility to a pathogen may be affected differently, yet in a parallel manner, by a present, as opposed to parental, dietary conditions. For example, it is possible that parental diet affects more strongly mechanisms that regulate an individual's ability to survive with a given pathogen load (tolerance mechanisms) than mechanisms that fight the pathogens directly (resistance mechanisms) (Schneider & Ayres, 2008). This could manifest as longer mean survival time in offspring with low-nutrition maternal diet. "
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    ABSTRACT: In addition to nutritional conditions experienced by individuals themselves, those experienced by their parents can affect their immune function. Here, we studied the intra- and trans-generational effects of larval diet on susceptibility to an entomopathogenic fungus, Beauveria bassiana, in the greater wax moth, Galleria mellonella. In the first part of the study, a split-brood design was used to compare the susceptibility of full-sibs raised either on low or high nutrition larval diet. In the second part of the study, a similar experimental design was employed to investigate the effects of maternal and paternal diet as well as their interaction on offspring's susceptibility. In the first part of the study, we found that individuals fed with high nutrition diet had higher mortality from infection than individuals fed with low nutrition diet. However, diet did not affect post-infection survival time. Conversely, in the second part of the study, maternal diet was found to have no significant effect on final mortality rate of offspring, but it affected survival time: larvae with high nutrition maternal diet survived fewer days after infection than larvae with low nutrition maternal diet. Paternal diet had no significant effect on offspring's susceptibility to the fungus, indicating that paternal effects are not as important as maternal effects in influencing immune function in this species. Our findings provide further indication that maternal nutrition affects immune function in insects, and suggest that the direct effects of nutrition on immunity may be different, yet parallel, to those caused by parental nutrition. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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