Hawash, M. B. F., M. A. El-Deeb, R. Gaber, and K. S. Morsy, "The buried gems of disease tolerance in animals: Evolutionary and interspecies comparative approaches: ", BioEssays : news and reviews in molecular, cellular and developmental biology, vol. 44, issue 10, pp. e2200080, 2022. Abstract

Host defense mechanisms are categorized into different strategies, namely, avoidance, resistance and tolerance. Resistance encompasses mechanisms that directly kill the pathogen while tolerance is mainly concerned with alleviating the harsh consequences of the infection regardless of the pathogen burden. Resistance is well-known strategy in immunology while tolerance is relatively new. Studies addressed tolerance mainly using mouse models revealing a wide range of interesting tolerance mechanisms. Herein, we aim to emphasize on the interspecies comparative approaches to explore potential new mechanisms of disease tolerance. We will discuss mechanisms of tolerance with focus on those that were revealed using comparative study designs of mammals followed by summarizing the reasons for adopting comparative approaches on disease tolerance studies. Disease tolerance is a relatively new concept in immunology, we believe combining comparative studies with model organism study designs will enhance our understanding to tolerance and unveil new mechanisms of tolerance.

Hawash, M. B. F., J. Sanz-Remón, J. - C. Grenier, J. Kohn, V. Yotova, Z. Johnson, R. E. Lanford, J. F. Brinkworth, and L. B. Barreiro, "Primate innate immune responses to bacterial and viral pathogens reveals an evolutionary trade-off between strength and specificity.", Proceedings of the National Academy of Sciences of the United States of America, vol. 118, issue 13, 2021. Abstract

Despite their close genetic relatedness, apes and African and Asian monkeys (AAMs) differ in their susceptibility to severe bacterial and viral infections that are important causes of human disease. Such differences between humans and other primates are thought to be a result, at least in part, of interspecies differences in immune response to infection. However, because of the lack of comparative functional data across species, it remains unclear in what ways the immune systems of humans and other primates differ. Here, we report the whole-genome transcriptomic responses of ape species (human and chimpanzee) and AAMs (rhesus macaque and baboon) to bacterial and viral stimulation. We find stark differences in the responsiveness of these groups, with apes mounting a markedly stronger early transcriptional response to both viral and bacterial stimulation, altering the transcription of ∼40% more genes than AAMs. Additionally, we find that genes involved in the regulation of inflammatory and interferon responses show the most divergent early transcriptional responses across primates and that this divergence is attenuated over time. Finally, we find that relative to AAMs, apes engage a much less specific immune response to different classes of pathogens during the early hours of infection, up-regulating genes typical of anti-viral and anti-bacterial responses regardless of the nature of the stimulus. Overall, these findings suggest apes exhibit increased sensitivity to bacterial and viral immune stimulation, activating a broader array of defense molecules that may be beneficial for early pathogen killing at the potential cost of increased energy expenditure and tissue damage.

FahmyHawash, M. B., AzmiAl-Jubury, M. EvaSengupta, T. V. AlstrupHansen, S. MilanThamsborg, and P. Nejsum, "Evidence for mitochondrial pseudogenes (numts) as a source of contamination in the phylogeny of human whipworms", Infection, Genetics and Evolution, vol. 86, 2020.
Nejsum, P., M. B. F. Hawash, M. Betson, R. J. Stothard, R. B. Gasser, and L. O. Andersen, "Ascaris phylogeny based on multiple whole mtDNA genomes", Infection, Genetics and Evolution, vol. 48, pp. 4-9, 2017.
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