Age-dependent virulence of human pathogens.

Host age is often evoked as an intrinsic factor aggravating the outcome of host-pathogen interactions. However, the shape of the relationship between age and infection-induced mortality might differ among pathogens, with specific clinical and ecological traits making some pathogens more likely to exert higher mortality in older hosts. Here, we used a large dataset on age-specific case fatality rate (CFR) of 28 human infectious diseases to investigate i) whether age is consistently associated to increased CFR, ii) whether pathogen characteristics might explain higher CFR in older adults. We found that, for most of the infectious diseases considered here, CFR slightly decreased during the first years of life and then steeply increased in older adults. Pathogens inducing diseases with long-lasting symptoms had the steepest increase of age-dependent CFR. Similarly, bacterial diseases and emerging viruses were associated with increasing mortality risk in the oldest age classes. On the contrary, we did not find evidence suggesting that systemic infections have steeper slopes between CFR and age; similarly, the relationship between age and CFR did not differ according to the pathogen transmission mode. Overall, our analysis shows that age is a key trait affecting infection-induced mortality rate in humans, and that the extent of the aggravating effect on older adults depends on some key traits, such as the duration of illness.

Paternal age negatively affects sperm production of the progeny.

Parental age has profound consequences for offspring's phenotype. However, whether patrilineal age affects offspring sperm production remains unknown, despite the importance of sperm production for male reproductive success in species facing post-copulatory sexual selection. Using a longitudinal dataset on ejaculate attributes of the houbara bustard, we showed that offspring sired by old fathers had different age-dependent trajectories of sperm production compared to offspring sired by young fathers. Specifically, they produced less sperm (-48%) in their first year of life, and 14% less during their lifetime. Paternal age had the strongest effect, with weak evidence for grandpaternal or great grandpaternal age effects. These results show that paternal age can affect offspring reproductive success by reducing sperm production, establishing an intergenerational link between ageing and sexual selection.

Development and optimization of a hybridization technique to type the classical class I and class II B genes of the chicken MHC.

The classical class I and class II molecules of the major histocompatibility complex (MHC) play crucial roles in immune responses to infectious pathogens and vaccines as well as being important for autoimmunity, allergy, cancer and reproduction. These classical MHC genes are the most polymorphic known, with roughly 10,000 alleles in humans. In chickens, the MHC (also known as the BF-BL region) determines decisive resistance and susceptibility to infectious pathogens, but relatively few MHC alleles and haplotypes have been described in any detail. We describe a typing protocol for classical chicken class I (BF) and class II B (BLB) genes based on a hybridization method called reference strand-mediated conformational analysis (RSCA). We optimize the various steps, validate the analysis using well-characterized chicken MHC haplotypes, apply the system to type some experimental lines and discover a new chicken class I allele. This work establishes a basis for typing the MHC genes of chickens worldwide and provides an opportunity to correlate with microsatellite and with single nucleotide polymorphism (SNP) typing for approaches involving imputation.

Post-copulatory sexual selection allows females to alleviate the fitness costs incurred when mating with senescing males.

Male senescence has detrimental effects on reproductive success and offspring fitness. When females mate with multiple males during the same reproductive bout, post-copulatory sexual selection that operates either through sperm competition or cryptic female choice might allow females to skew fertilization success towards young males and as such limit the fitness costs incurred when eggs are fertilized by senescing males. Here, we experimentally tested this hypothesis. We artificially inseminated female North African houbara bustards with sperm from dyads of males of different (young and old) or similar ages (either young or old). Then, we assessed whether siring success was biased towards young males and we measured several life-history traits of the progeny to evaluate the fitness costs due to advanced paternal age. In agreement with the prediction, we found that siring success was biased towards young males, and offspring sired by old males had impaired hatching success, growth and post-release survival (in females). Overall, our results support the hypothesis that post-copulatory sexual selection might represent an effective mechanism allowing females to avoid the fitness costs of fertilization by senescing partners.

Sperm competition accentuates selection on ejaculate attributes.

Ejaculate attributes are important factors driving the probability of fertilizing eggs. When females mate with several males, competition between sperm to fertilize eggs should accentuate selection on ejaculate attributes. We tested this hypothesis in the North African houbara bustard ( Chlamydotis undulata undulata) by comparing the strength of selection acting on two ejaculate attributes when sperm from single males or sperm from different males were used for insemination. In agreement with the prediction, we found that selection on ejaculate attributes was stronger when sperm of different males competed for egg fertilization. These findings provide the first direct comparison of the strength of selection acting on ejaculate attributes under competitive and non-competitive fertilizations, confirming that sperm competition is a major selective force driving the evolution of ejaculate characteristics.

Age-related response to an acute innate immune challenge in mice: proteomics reveals a telomere maintenance-related cost.

Ageing is characterized by the impairment of the acute innate immune response and the upregulation of low-grade inflammation, i.e. inflammaging. At the cellular level, telomeres are considered as a marker of biological ageing as their length is progressively eroded in the absence of repair mechanisms. However, the link between telomeres and inflammaging remains underexplored. We aimed to identify proteins that are differentially expressed between age classes in response to an acute inflammatory challenge. We challenged young (two months) and old (12 months) C57BL/6 mice using bacterial lipopolysaccharide (LPS) and measured telomere length and proteomic profiles in splenocytes. In total, 233 out of the 1966 proteins we quantified differed among experimental groups. A hierarchical clustering analysis revealed that nine of those 233 proteins were differently expressed among the experimental groups. Young mice responded to LPS by increasing the expression of proteins involved in the innate immune response, and interestingly, in telomere length maintenance. However, this regulation was impaired at older ages. These results are in agreement with the assumption that the strength of selection declines with age, potentially explaining the maintenance of costly, dysregulated, immune responses at old age. We suggest that the immune response is competing with the telomere maintenance process, highlighting how telomeres reflect the ageing trade-off even in a species where telomere length is not related to lifespan.

No evidence for prezygotic postcopulatory avoidance of kin despite high inbreeding depression.

Offspring resulting from mating among close relatives can suffer from impaired fitness through the expression of recessive alleles with deleterious effects. Postcopulatory sperm selection (a prezygotic mechanism of cryptic female choice) has been suggested to be an effective way to avoid inbreeding. To investigate whether postcopulatory female choice allows the avoidance of fertilization by close kin, we performed artificial inseminations in a promiscuous bird, the houbara bustard (Chlamydotis undulata undulata). Females were inseminated with a mix of sperm from triads of males, each constituted of a male genetically unrelated to the female, a first cousin and a half-sibling. When counting the number of eggs sired by unrelated males, cousins or half-siblings, we found a significant deviation from the expected random distribution, with more eggs sired by unrelated males. However, offspring sired by cousins, and especially by half-siblings suffered from high prehatching mortality, suggesting that the observed paternity skew towards unrelated males might reflect differential offspring mortality rather than sperm selection. In agreement with this hypothesis, within-triad siring success was similar for the three parental relatedness categories, but the relationship between siring and hatching success differed across categories. In clutches with high hatching success, unrelated males had the highest success while in clutches with high failure rate, half-siblings had the highest success. Offspring sired by half-siblings also suffered from reduced growth rate during the first three months and higher posthatching mortality. Hence, despite substantial fitness costs associated with fertilization by close relatives, females do not seem to select sperm of unrelated males.

Infections and cancer: the "fifty shades of immunity" hypothesis.

BACKGROUND: Since the beginning of the twentieth century, infection has emerged as a fundamental aspect of cancer causation with a growing number of pathogens recognized as oncogenic. Meanwhile, oncolytic viruses have also attracted considerable interest as possible agents of tumor destruction. DISCUSSION: Lost in the dichotomy between oncogenic and oncolytic agents, the indirect influence of infectious organisms on carcinogenesis has been largely unexplored. We describe the various ways - from functional aspects to evolutionary considerations such as modernity mismatches - by which infectious organisms could interfere with oncogenic processes through immunity. Finally, we discuss how acknowledging these interactions might impact public health approaches and suggest new guidelines for therapeutic and preventive strategies both at individual and population levels. Infectious organisms, that are not oncogenic neither oncolytic, may play a significant role in carcinogenesis, suggesting the need to increase our knowledge about immune interactions between infections and cancer.

Life history adjustments to intestinal inflammation in a gut nematode.

Many parasitic nematodes establish chronic infections. This implies a finely tuned interaction with the host immune response in order to avoid infection clearance. Although a number of immune interference mechanisms have been described in nematodes, how parasites adapt to the immune environment provided by their hosts remains largely unexplored. Here, we used the gastrointestinal nematode Heligmosomoides polygyrus to investigate the plasticity of life history traits and immunomodulatory mechanisms in response to intestinal inflammation. We adopted an experimental model of induced colitis and exposed worms to intestinal inflammation at two different developmental stages (larvae and adults). We found that H. polygyrus responded to intestinal inflammation by up-regulating the expression of a candidate gene involved in the interference with the host immune response. Worms infecting mice with colitis also had better infectivity (earlier adult emergence in the intestinal lumen and higher survival) compared with worms infecting control hosts, suggesting that H. polygyrus adjusted its life history schedule in response to intestinal inflammation.

Aging parasites produce offspring with poor fitness prospects.

Senescing individuals have poor survival prospects and low fecundity. They can also produce offspring with reduced survival and reproductive success. We tested the effect of parental age on the performance of descendants in the nematode Heligmosomoides polygyrus, an intestinal parasite of rodents. We found that offspring of senescing worms had reduced within-host survival and reduced egg shedding over the first month post-infection compared with offspring produced by young parents. These results suggest that declining offspring quality is a component of senescence in parasitic nematodes and might have evolutionary consequences for the optimal schedule of age-dependent investment into reproductive effort.

Plastic and micro-evolutionary responses of a nematode to the host immune environment.

Parasitic organisms have to cope with the defences deployed by their hosts and this can be achieved adopting immune evasion strategies or optimal life history traits according to the prevailing pattern of immune-mediated mortality. Parasites often encounter variable immune environments both within and between hosts, promoting the evolution of plastic strategies instead of fixed responses. Here, we explored the plasticity and micro-evolutionary responses of immunomodulatory mechanisms and life history traits to the immune environment provided by the host, using the parasitic nematode Heligmosomoides polygyrus. To test if the parasite responds plastically to the immune environment, we stimulated the systemic inflammatory response of mice and we assessed i) the expression of two genes with candidate immunomodulatory functions (Hp-Tgh2 and Hp-CPI); ii) changes in the number of eggs shed in the faeces. To test if the immune environment induces a micro-evolutionary response in the parasite, we maintained the nematode in mice whose inflammatory response was up- or down-regulated during four generations. We found that H. polygyrus plastically responded to a sudden rise of pro-inflammatory cytokines, up-regulating the expression of two candidate genes involved in the process of immune modulation, and enhancing egg output. At the micro-evolutionary level, parasites maintained in hosts experiencing different levels of inflammation did not have differential expression of Hp-Tgh2 and Hp-CPI genes when infecting unmanipulated, control, mice. However, parasites maintained in mice with an up-regulated inflammation shed more eggs compared to the control line. Overall, our study shows that H. polygyrus can plastically adjust the expression of immunomodulatory genes and life history traits, and responds to selection exerted by the host immune system.

Helminth Interaction with the Host Immune System: Short-Term Benefits and Costs in Relation to the Infectious Environment.

Chronic infections imply that the parasite and the host immune system closely interact for a long time without a fatal outcome. Environmental changes encountered by hosts and parasites, such as coinfections, can deeply affect the stability of this apparent equilibrium. Our study aimed to determine the effect of the infectious environment on the costs and benefits of chronic infection with the gut nematode Heligmosomoides polygyrus in mice. Heligmosomoides polygyrus is known for its capacity to actively interfere with the host immune response by secreting molecules that can dampen immunity. We simulated bacterial coinfection of H. polygyrus-infected CBA-strain mice during the chronic phase of the infection by injecting them with Escherichia coli lipopolysaccharide. We found that infection by H. polygyrus induced only weak costs for the host (in terms of reproductive investment) and was characterized by the upregulation of both Th1 (interferon-γ) and anti-inflammatory (transforming growth factor-ß) cytokines, which is favorable to parasite persistence. However, when co-occurring with the simulated bacterial infection, H. polygyrus infection was associated with a pronounced shift toward a pro-inflammatory status, which was deleterious to both the parasite and the host. Our study highlights the dynamic equilibrium reached during chronic infection, where a rapid environmental change, such as a concomitant bacterial infection, can deeply affect the outcome of the host-parasite interaction.

Females tend to prefer genetically similar mates in an island population of house sparrows.

BACKGROUND: It is often proposed that females should select genetically dissimilar mates to maximize offspring genetic diversity and avoid inbreeding. Several recent studies have provided mixed evidence, however, and in some instances females seem to prefer genetically similar males. A preference for genetically similar mates can be adaptive if outbreeding depression is more harmful than inbreeding depression or if females gain inclusive fitness benefits by mating with close kin. Here, we investigated genetic compatibility and mating patterns in an insular population of house sparrow (Passer domesticus), over a three-year period, using 12 microsatellite markers and one major histocompability complex (MHC) class I gene. Given the small population size and the distance from the mainland, we expected a reduced gene flow in this insular population and we predicted that females would show mating preferences for genetically dissimilar mates. RESULTS: Contrary to our expectation, we found that offspring were less genetically diverse (multi-locus heterozygosity) than expected under a random mating, suggesting that females tended to mate with genetically similar males. We found high levels of extra-pair paternity, and offspring sired by extra-pair males had a better fledging success than those sired by the social male. Again, unexpectedly, females tended to be more closely related to extra-pair mates than to their social mates. Our results did not depend on the type of genetic marker used, since microsatellites and MHC genes provided similar results, and we found only little evidence for MHC-dependent mating patterns. CONCLUSIONS: These results are in agreement with the idea that mating with genetically similar mates can either avoid the disruption of co-adapted genes or confer a benefit in terms of kin selection.

Parental experience of a risky environment leads to improved offspring growth rate.

Parasites (or diseases) are a major selective force for the evolution of life history traits and parasite-host evolution. Mothers can show a variety of responses to parasites during pregnancy, with different consequences for them or their offspring. However, whether information in the maternal environment before pregnancy can cause a change in the phenotype of the offspring is unknown. To avoid the confounding effect of pathogens and to reduce the risk of a direct effect of maternal immune system activation, we injected female laboratory mice with lipopolysaccharides (LPS) before they mated. In order to provide constant information on the potential infectious risk of the environment, females were mated with males that were also exposed to LPS before mating. Offspring from immune-challenged parents were larger and grew at a faster rate than offspring from control parents (injected with PBS). Additionally, offspring from immune-challenged parents that suffered the most from inflammation grew at a faster rate than offspring from low suffering parents. Producing heavier offspring that will reach sexual maturity earlier is likely to have fitness benefits for parents and offspring through improved reproductive success.

Impact of host nutritional status on infection dynamics and parasite virulence in a bird-malaria system.

Host resources can drive the optimal parasite exploitation strategy by offering a good or a poor environment to pathogens. Hosts living in resource-rich habitats might offer a favourable environment to developing parasites because they provide a wealth of resources. However, hosts living in resource-rich habitats might afford a higher investment into costly immune defences providing an effective barrier against infection. Understanding how parasites can adapt to hosts living in habitats of different quality is a major challenge in the light of the current human-driven environmental changes. We studied the role of nutritional resources as a source of phenotypic variation in host exploitation by the avian malaria parasite Plasmodium relictum. We investigated how the nutritional status of birds altered parasite within-host dynamics and virulence, and how the interaction between past and current environments experienced by the parasite accounts for the variation in the infection dynamics. Experimentally infected canaries were allocated to control or supplemented diets. Plasmodium parasites experiencing the two different environments were subsequently transmitted in a full-factorial design to new hosts reared under similar control or supplemented diets. Food supplementation was effective since supplemented hosts gained body mass during a 15-day period that preceded the infection. Host nutrition had strong effects on infection dynamics and parasite virulence. Overall, parasites were more successful in control nonsupplemented birds, reaching larger population sizes and producing more sexual (transmissible) stages. However, supplemented hosts paid a higher cost of infection, and when keeping parasitaemia constant, they had lower haematocrit than control hosts. Parasites grown on control hosts were better able to exploit the subsequent hosts since they reached higher parasitaemia than parasites originating from supplemented hosts. They were also more virulent since they induced higher mass and haematocrit loss. Our study highlights that parasite virulence can be shaped by the host nutritional status and that parasite can adapt to the environment provided by their hosts, possibly through genetic selection.

Multiple aspects of plasticity in clutch size vary among populations of a globally distributed songbird.

Plasticity in life-history characteristics can influence many ecological and evolutionary phenomena, including how invading organisms cope with novel conditions in new locations or how environmental change affects organisms in native locations. Variation in reaction norm attributes is a critical element to understanding plasticity in life history, yet we know relatively little about the ways in which reaction norms vary within and among populations. We amassed data on clutch size from marked females in eight populations of house sparrows (Passer domesticus) from North America and Europe. We exploited repeated measures of clutch size to assess both the extent of within-individual phenotypic plasticity and among-individual variation and to test alternative hypotheses about the underlying causes of reaction norm shape, particularly the decline in clutch size with date. Across all populations, females of this multibrooded species altered their clutch size with respect to date, attempt order, and the interaction of date and order, producing a reaction norm in multidimensional environmental space. The reaction norm fits that predicted by a model in which optimal clutch size is driven by a decline with date hatched in the ability of offspring to recruit. Our results do not fit those predicted for other proposed causes of a seasonal decline in clutch size. We also found significant differences between populations in response to date and the date by attempt order interaction. We tested the prediction that the relationship with date should be increasingly negative as breeding season becomes shorter but found steeper declines in clutch size with date in populations with longer seasons, contrary to the prediction. Populations also differed in the level of among-individual variation in reaction norm intercept, but we found no evidence of among-individual variation in reaction norm slope. We show that complex reaction norms in life-history characters exhibit within- and among-population variance. The nature of this variance is only partially consistent with current life-history theory and stimulates expansions of such theory to accommodate complexities in adaptive life history.

Oxidative stress in relation to reproduction, contaminants, gender and age in a long-lived seabird.

Reproduction is a demanding activity for animals, since they must produce, and in some cases protect and provision, their young. It is often overlooked that demands of reproduction may also be exacerbated by exposure to contaminants. In this study, we make use of an exceptional long-term dataset to perform a cross-sectional study on the long-lived wandering albatross (Diomedea exulans) in order to test the effects of reproduction, persistent organic pollutants [POPs: pesticides and polychlorinated biphenyls (PCBs)], mercury, individual age (3-47 years), and sex on the levels of plasma oxidative damage and inflammation. The results of our study support the hypothesis that oxidative damage may be a physiological cost of reproduction and that individuals carrying higher levels of organic or non-organic contaminants have higher oxidative damage. Levels of the inflammatory protein haptoglobin were similar between breeding and non-breeding birds, with the exception of breeding males which had the lowest levels of haptoglobin. Our data also show an effect of age and of organic contaminants on the plasma oxidative damage level, but not on plasma haptoglobin. In addition, plasma oxidative damage level increased with red blood cell mercury concentration in females but not in males. Hence, our study highlights that the harmful effects of contaminants may come through interaction with factors like life stage or gender, suggesting potential for high variation in susceptibility to contamination among individuals.

Social inequalities and the COVID-19 pandemic.

Social inequality has been identified as an important determinant of the outcome of infectious diseases and the recent SARS-CoV-2 pandemic has vividly reminded us that there are no "equal opportunity infectors". In a recent article, Chakrabarty et al. (2023) reported the finding of a cross-country comparison of COVID-19 cases and social deprivation, using up-to-date statistical modelling. These results add to the extensive evidence showing that vulnerable populations are consistently at higher risk of contracting the infection and to suffer from more severe symptoms, whatever the spatial scale used (from the country to the neighborhood). Spatial clustering of socially deprived groups, preexisting pathologies and hotspots of COVID-19 cases and deaths indicate that the SARS-CoV-2 should be seen as a syndemic, where both the infection dynamics and the outcome of the disease strongly depend on the three-way interaction between the virus, preexisting pathologies, and the socioeconomic environment.

Diet modulates strongyle infection and microbiota in the large intestine of horses.

The use of anthelminthic drugs has several drawbacks, including the selection of resistant parasite strains. Alternative avenues to mitigate the negative effects of helminth infection involve dietary interventions that might affect resistance and/or tolerance by improving host immunity, modulating the microbiota, or exerting direct anthelmintic effects. The aim of this study was to assess the impact of diet on strongyle infection in horses, specifically through immune-mediated, microbiota-mediated, or direct anthelmintic effects. Horses that were naturally infected with strongyles were fed either a high-fiber or high-starch diet, supplemented with either polyphenol-rich pellets (dehydrated sainfoin) or control pellets (sunflower and hay). When horses were fed a high-starch diet, they excreted more strongyle eggs. Adding sainfoin in the high-starch diet reduced egg excretion. Additionally, sainfoin decreased larval motility whatever the diet. Moreover, the high-starch diet led to a lower fecal bacterial diversity, structural differences in fecal microbiota, lower fecal pH, lower blood acetate, and lower hematocrit compared to the high-fiber diet. Circulating levels of Th1 and Th2 cytokines, lipopolysaccharides, procalcitonin, and white blood cells proportions did not differ between diets. Overall, this study highlights the role of dietary manipulations as an alternative strategy to mitigate the effect of helminth infection and suggests that, in addition to the direct effects, changes in the intestinal ecosystem are the possible underlying mechanism.

Positive psychological effects of seated acupressure massage are associated with a rise in plasma oxytocin without affecting CGRP levels or circulating IL-6.

Work-related stress is a major public health issue. Given the relationship between acute stress responses and health, finding strategies to deal with the unpleasant symptoms brought on by stress is essential. Massage therapy is a popular stress-reduction technique, but its effectiveness has yet to be shown. In that matter, this study investigates the effects of a 17-minute session of seated Amma massage on young healthy people. Subjective stress perception, anxiety and self-confidence were assessed before and after the massage using the Spielberger State Anxiety Scale (STAI-Y, Spielberger et al., 1983) and the Competitive State Anxiety Inventory (EEAC, Cury et al., 1999), together with cardiovascular parameters. Cortisol, CGRP, IL-6, and oxytocin plasma levels were measured before and after the massage to investigate its possible mode of action. This study enrolled 59 people: 33 receiving the massage, and 26 controls only seated on the massage chair. Interaction Time x Group demonstrates significant differences for all psychological measurements (STAI, EEAC) before and after the Amma massage, showing a beneficial effect of this treatment, in particular on perceived anxiety and self-confidence. No evidence was found of any correlation between cortisol plasma levels and psychological outcomes. No relationship was shown between the decrease of perceived stress and measured CGRP or IL-6 release, but the data demonstrated that heart frequency could be slightly decreased. The oxytocin plasma levels were significantly increased by the massage and could be responsible for the recovery of psychological outcomes. We conclude that seated acupressure Amma massage could be a useful tool to ameliorate quality of life at work.