An offer you cannot refuse: down-regulation of immunity in response to a pathogen's retaliation threat.

According to the Red Queen hypothesis, hosts and pathogens are engaged in an escalating coevolutionary arms race between resistance and virulence. However, the vast majority of symbionts colonize their hosts' mucosal compartments without triggering any immune response, resulting in durable commensal associations. Here, I propose a simple extension of previous mathematical models for antagonistic coevolution in which the host can mount a delayed immune response; in response, the symbiont can change its virulence following this activation. Even though the levels of virulence in both phases are assumed to be genetically determined, this simple form of plasticity can select for commensal associations. In particular, coevolution can result in hosts that do not activate their immune response, thus preventing phenotypically plastic pathogens from switching to a higher virulence level. I argue that, from the host's point of view, this state is analogous to the mafia behaviour previously described in avian brood parasites. More importantly, this study provides a new hypothesis for the maintenance of a commensal relationship through antagonistic coevolution

Within-host dynamics of infection: from ecological insights to evolutionary predictions.

O.R. is supported by a University Research Fellowship from The Royal Society.This is the final version of the article. It first appeared from Royal Society Publishing via http://dx.doi.org/10.1098/rstb.2014.030

The evolution of sex-specific immune defences

Why do males and females often differ in their ability to cope with infection? Beyond physiological mechanisms, it has recently been proposed that life-history theory could explain immune differences from an adaptive point of view in relation to sex-specific reproductive strategies. However, a point often overlooked is that the benefits of immunity, and possibly the costs, depend not only on the host genotype but also on the presence and the phenotype of pathogens. To address this issue we developed an adaptive dynamic model that includes host–pathogen population dynamics and host sexual reproduction. Our model predicts that, although different reproductive strategies, following Bateman's principle, are not enough to select for different levels of immunity, males and females respond differently to further changes in the characteristics of either sex. For example, if males are more exposed to infection than females (e.g. for behavioural reasons), it is possible to see them evolve lower immunocompetence than females. This and other counterintuitive results highlight the importance of ecological feedbacks in the evolution of immune defences. While this study focuses on sex-specific natural selection, it could easily be extended to include sexual selection and thus help to understand the interplay between the two processes

Spread and transmission of bacterial pathogens in experimental populations of the nematode Caenorhabditis elegans.

Caenorhabditis elegans is frequently used as a model species for the study of bacterial virulence and innate immunity. In recent years, diverse mechanisms contributing to the nematode's immune response to bacterial infection have been discovered. Yet despite growing interest in the biochemical and molecular basis of nematode-bacterium associations, many questions remain about their ecology. Although recent studies have demonstrated that free-living nematodes could act as vectors of opportunistic pathogens in soil, the extent to which worms may contribute to the persistence and spread of these bacteria has not been quantified. We conducted a series of experiments to test whether colonization of and transmission between C. elegans nematodes could enable two opportunistic pathogens (Salmonella enterica and Pseudomonas aeruginosa) to spread on agar plates occupied by Escherichia coli. We monitored the transmission of S. enterica and P. aeruginosa from single infected nematodes to their progeny and measured bacterial loads both within worms and on the plates. In particular, we analyzed three factors affecting the dynamics of bacteria: (i) initial source of the bacteria, (ii) bacterial species, and (iii) feeding behavior of the host. Results demonstrate that worms increased the spread of bacteria through shedding and transmission. Furthermore, we found that despite P. aeruginosa's relatively high transmission rate among worms, its pathogenic effects reduced the overall number of worms colonized. This study opens new avenues to understand the role of nematodes in the epidemiology and evolution of pathogenic bacteria in the environment.Some C. elegans and bacteria strains were provided by the Caenorhabditis Genetics Centre, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). We thank Andrew Grant and Craig Winstanley for providing strains and reagents. We thank Mark Viney and two anonymous reviewers for helpful comments on the manuscript. This research was funded by a grant from the Biotechnology and Biological Sciences Research Council (grant number BB/I012222/1) to OR. OR also acknowledges funding from the Royal Society (University Research Fellowship).This is the author accepted manuscript. The final published version can be found on the publisher's website at: http://aem.asm.org/content/early/2014/06/23/AEM.01037-14.long Copyright © 2014, American Society for Microbiology. All Rights Reserve

An experimental design tool to optimize inference precision in data-driven mathematical models of bacterial infections in vivo.

The management of bacterial diseases calls for a detailed knowledge about the dynamic changes in host-bacteria interactions. Biological insights are gained by integrating experimental data with mechanistic mathematical models to infer experimentally unobservable quantities. This inter-disciplinary field would benefit from experiments with maximal information content yielding high-precision inference. Here, we present a computationally efficient tool for optimizing experimental design in terms of parameter inference in studies using isogenic-tagged strains. We study the effect of three experimental design factors: number of biological replicates, sampling timepoint selection and number of copies per tagged strain. We conduct a simulation study to establish the relationship between our optimality criterion and the size of parameter estimate confidence intervals, and showcase its application in a range of biological scenarios reflecting different dynamics patterns observed in experimental infections. We show that in low-variance systems with low killing and replication rates, predicting high-precision experimental designs is consistently achieved; higher replicate sizes and strategic timepoint selection yield more precise estimates. Finally, we address the question of resource allocation under constraints; given a fixed number of host animals and a constraint on total inoculum size per host, infections with fewer strains at higher copies per strain lead to higher-precision inference

Integrating mathematical models with experimental data to investigate the within-host dynamics of bacterial infections.

Bacterial infections still constitute a major cause of mortality and morbidity worldwide. The unavailability of therapeutics, antimicrobial resistance and the chronicity of infections due to incomplete clearance contribute to this phenomenon. Despite the progress in antimicrobial and vaccine development, knowledge about the effect that therapeutics have on the host-bacteria interactions remains incomplete. Insights into the characteristics of bacterial colonization and migration between tissues and the relationship between replication and host- or therapeutically induced killing can enable efficient design of treatment approaches. Recently, innovative experimental techniques have generated data enabling the qualitative characterization of aspects of bacterial dynamics. Here, we argue that mathematical modeling as an adjunct to experimental data can enrich the biological insight that these data provide. However, due to limited interdisciplinary training, efforts to combine the two remain limited. To promote this dialogue, we provide a categorization of modeling approaches highlighting their relationship to data generated by a range of experimental techniques in the area of in vivo bacterial dynamics. We outline common biological themes explored using mathematical models with case studies across all pathogen classes. Finally, this review advocates multidisciplinary integration to improve our mechanistic understanding of bacterial infections and guide the use of existing or new therapies

Yves Tourenne, Les conditions fondamentales de la prière. Métaphysique et prière chez Claude Tresmontant

Cet ouvrage, écrit par le franciscain Yves Tourenne, docteur en théologie et en philosophie, s’appuie sur l’œuvre de Claude Tresmontant, professeur de philosophie décédé en 1997, pour montrer en quoi la métaphysique détermine les conditions de la prière. L’objectif paraît séducteur et l’on s’attend à trouver d’une part une analyse partiellement critique de l’œuvre de Tresmontant et d’autre part une véritable métaphysique de la prière. La préface rédigée par Monseigneur Marc Aillet, évêque de ..

Challenges in modelling the dynamics of infectious diseases at the wildlife-human interface.

Funder: Alborada TrustThe Covid-19 pandemic is of zoonotic origin, and many other emerging infections of humans have their origin in an animal host population. We review the challenges involved in modelling the dynamics of wildlife-human interfaces governing infectious disease emergence and spread. We argue that we need a better understanding of the dynamic nature of such interfaces, the underpinning diversity of pathogens and host-pathogen association networks, and the scales and frequencies at which environmental conditions enable spillover and host shifting from animals to humans to occur. The major drivers of the emergence of zoonoses are anthropogenic, including the global change in climate and land use. These, and other ecological processes pose challenges that must be overcome to counterbalance pandemic risk. The development of more detailed and nuanced models will provide better tools for analysing and understanding infectious disease emergence and spread

Éric Durot, François de Lorraine, duc de Guise entre Dieu et le Roi

C’est une véritable somme que nous livre Éric Durot, tirée de sa thèse de doctorat soutenue sous la direction de Denis Crouzet en 2011, sur cette figure centrale du xvie siècle qu’est le second duc de Guise, assassiné en 1563. Cet ouvrage est donc d’abord la biographie qui manquait tant sur ce personnage majeur, mais il est aussi plus que cela, de nombreux développements étant consacrés aux contextes changeants dans lesquels évolue François de Lorraine. Les lecteurs de Denis Crouzet reconnaît..

Éric Durot, François de Lorraine, duc de Guise entre Dieu et le Roi

C’est une véritable somme que nous livre Éric Durot, tirée de sa thèse de doctorat soutenue sous la direction de Denis Crouzet en 2011, sur cette figure centrale du xvie siècle qu’est le second duc de Guise, assassiné en 1563. Cet ouvrage est donc d’abord la biographie qui manquait tant sur ce personnage majeur, mais il est aussi plus que cela, de nombreux développements étant consacrés aux contextes changeants dans lesquels évolue François de Lorraine. Les lecteurs de Denis Crouzet reconnaît..