Disentangling Human Tolerance and Resistance Against HIV

Regoes, Roland R.; McLaren, Paul J.; Battegay, Manuel; Bernasconi, Enos; Calmy, Alexandra; Günthard, Huldrych F.; Hoffmann, Matthias; Rauch, Andri; Telenti, Amalio; Fellay, Jacques

doi:10.1371/journal.pbio.1001951

Cited by 57 publications

(101 citation statements)

References 47 publications

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“…As network topology is known to affect virulence evolution (van Baalen, ), capturing all these details with a single parameter ( h ) is likely to be too oversimplifying to draw results applicable to HIV. Second, a recent study that tried to disentangle resistance from tolerance in HIV infections found no differences between host sexes (Regoes et al ., ). Finally, in our model, we did not vary resistance and tolerance simultaneously.…”

Section: Discussionmentioning

confidence: 99%

Parasite evolution in response to sex‐based host heterogeneity in resistance and tolerance

Cousineau

Alizon

2014

J of Evolutionary Biology

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Heterogenity between sexes in terms of both the level and the type of immune response to infection is documented in many species, but its role on parasite evolution is only beginning to be explored. We adopt an evolutionary epidemiology approach to study how the ability of a host to respond to infection through active immunity (resistance) or through minimizing deleterious effects of a given parasite load (tolerance) affects the evolution of parasite virulence. Consistently with earlier models, we find that increases in host resistance and tolerance both favour more virulent parasite strains. However, we show that qualitatively different results can be obtained if dimorphism between the sexes occurs through resistance or through tolerance depending on the contact pattern between the sexes. Finally, we find that variations in host sex ratio can amplify the consequences of heterogeneity for parasite evolution. These results are analysed in the light of several examples from the literature to illustrate the prevalence of sexually dimorphic immune responses and the potential for further study of the role of sexual dimorphism on parasite evolution. Such studies are likely to be highly relevant for improving treatment of chronic infections and control of infectious diseases, and understanding the role of sex in immune function.

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Section: Discussionmentioning

confidence: 99%

Parasite evolution in response to sex‐based host heterogeneity in resistance and tolerance

Cousineau

Alizon

2014

J of Evolutionary Biology

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“…We used the Drosophila Oregon-R strain as an initial wild-type strain in our experiments. We chose to use a transplantable cancer model instead of an inducible one because it let us precisely regulate and measure input material (Ayres et al, 2008; Råberg et al, 2007; Regoes et al, 2014). We used the Ras v12 -H7 line of Drosophila hyperplastic cancer cells, which expresses an oncogenic form of Ras , has a UAS-GFP reporter, and has previously been shown to metastasize throughout the fly and lead to premature death (Simcox et al, 2008) (see Experimental Procedures).…”

Section: Resultsmentioning

confidence: 99%

Defining Resistance and Tolerance to Cancer

Dillman

2015

Cell Reports

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Summary There are two ways to maintain fitness in the face of infection: resistance is a host’s ability to reduce microbe load and disease tolerance is the ability of the host to endure the negative health effects of infection. Resistance and disease tolerance should be applicable to any insult to the host and have been explored in depth with regards to infection, but have not been examined in the context of cancer. Here, we establish a framework for measuring and separating resistance and disease tolerance to cancer in Drosophila melanogaster. We plot a disease tolerance curve to cancer in wild-type flies and then compare this to natural variants, identifying a line with reduced cancer resistance. Quantitation of these two traits opens an additional dimension for analysis of cancer biology.

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“…() presented a similar finding in mice infected with malaria. Other studies reported no correlation between tolerance and resistance in plants subjected to herbivores (Mauricio et al , ), in humans infected with HIV (Regoes et al , ) or in wild sheep infected with a parasite (Maze‐Guilmo et al , ). Interestingly, in Drosophila melanogaster populations exposed to a bacterial infection, tolerance and resistance exhibited a positive correlation (Howick & Lazzaro, ).…”

Section: Introductionmentioning

confidence: 95%

A tradeoff between tolerance and resistance to a major fungal pathogen in elite wheat cultivars

Mikaberidze

McDonald

2020

New Phytologist

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Summary Tolerance and resistance represent two strategies that hosts evolved to protect themselves from pathogens. Tolerance alleviates the reduction in host fitness due to infection without reducing a pathogen's growth, whereas resistance reduces pathogen growth. We investigated the tolerance of wheat to the major fungal pathogen Zymoseptoria tritici in 335 elite wheat cultivars. We used a novel digital phenotyping approach that included 11 152 infected leaves and counted 2069 048 pathogen fruiting bodies. We discovered a new component of tolerance that is based on the relationship between the green area remaining on a leaf and the number of pathogen fruiting bodies. We found a negative correlation between tolerance and resistance among intolerant cultivars, presenting the first compelling evidence for a tradeoff between tolerance and resistance to plant pathogens. Surprisingly, the tradeoff arises due to limits in the host resources available to the pathogen and not due to metabolic constraints, contrary to what ecological theory suggests. The mechanism underlying this tradeoff may be relevant for many plant diseases in which the amount of host resources available to the pathogen can limit the pathogen population. Our analysis indicates that European wheat breeders may have selected for tolerance instead of resistance to an important pathogen.

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Disentangling Human Tolerance and Resistance Against HIV

Abstract: Title: Human tolerance against HIV An evolutionary ecology perspective on clinical data reveals that human traits can affect how well an individual tolerates HIV infection, and identifies host immunity factors associated with disease tolerance.

Cited by 57 publications

References 47 publications

Parasite evolution in response to sex‐based host heterogeneity in resistance and tolerance

Parasite evolution in response to sex‐based host heterogeneity in resistance and tolerance

Defining Resistance and Tolerance to Cancer

A tradeoff between tolerance and resistance to a major fungal pathogen in elite wheat cultivars

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