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

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.     

Parasite spread in experimental metapopulations: resistance,tolerance and host competence

Host competence, defined as the likelihood that a host will transmit infection, may be affected by an individual's resistance to infection and its ability to withstand damage caused by infection (tolerance). Host competence may therefore be one of the most important factors to impact host–parasite dynamics, yet the relationships among resistance, tolerance and competence are poorly understood. The objective of the present study was to determine whether individual host resistance (ability to resist or minimize infection) and/or tolerance (ability to withstand or minimize reduction in fitness due to infection) contributed to the competence (ability to spread infection) of hosts using guppies infected with the ectoparasite, Gyrodactylus turnbulli. This individual-fish level analysis used data collected from a previous metapopulation experiment that had tracked host–parasite dynamics at the metapopulation scale using individually marked guppies that were moved among experimental tanks within replicate metapopulations. Fish tolerance was measured as the residual from a fish's expected survival post-infection for a given parasite burden. Fish resistance was measured as the peak parasite load (– log-transformed). Host competence was measured as the incidence (number of new infections over two days after the arrival of a fish to a tank) weighted by the density of available uninfected fish in the tank. In contrast to the assumption of a trade-off between resistance and tolerance, individual fish tolerance and resistance were both negatively associated with competence. Connectivity (the number of fish with which an individual came into contact) was not associated with competence. Our results indicate that resistance and tolerance are both important to disease spread. These findings highlight the importance of understanding how individual defence against parasites may contribute to its competence as a host, and therefore impact metapopulation-level dynamics.     

Natural variation in host feeding behaviors impacts host disease and pathogen transmission potential

Animals ranging from mosquitoes to humans often vary their feeding behavior when infected or merely exposed to pathogens. These so‐called “sickness behaviors” are part of the innate immune response with many consequences, including avoiding orally transmitted pathogens. Fully understanding the role of this ubiquitous behavior in host defense and pathogen evolution requires a quantitative account of its impact on host and pathogen fitness across environmentally relevant contexts. Here, we use a zooplankton host and fungal pathogen as a case study to ask if infection‐mediated feeding behaviors vary across pathogen exposure levels and natural genetic variation in susceptibility to infection. Then, we connect these changes in behavior to pathogen transmission potential (spore yield) and fitness and growth costs to the host. Our results validate a protective effect of altered feeding behavior during pathogen exposure while also revealing significant variation in the magnitude of this response across host susceptibility and pathogen exposure levels. Across all four host genotypes, feeding rates were negatively correlated with susceptibility to infection and transmission potential. The most susceptible genotypes exhibited either strong anorexia, reducing food intake by 26%–42%, (“Standard”) or pronounced hyperphagia, increasing food intake by 20%–54% (“A45”). Together, these results suggest that infection‐mediated changes in host feeding behavior—which are traditionally interpreted as immunopathology— may in fact serve as crucial components of host defense strategies and warrant further investigation.     

Within and transgenerational immune priming in an insect to a DNA virus

Invertebrates mount a sophisticated immune response with the potential to exhibit a form of immune memory through ‘priming’. Increased immune protection following early exposure to bacteria has been found both later in life (within generation priming) and in the next generation (transgeneration priming) in a number of invertebrates. However, it is unclear how general immune priming is and whether immune priming occurs in response to different parasites, including viruses. Here, using Plodia interpuctella (Lepidoptera) and its natural DNA virus, Plodia interpunctella granulosis virus, we find evidence for both within generation and transgeneration immune priming. Individuals previously exposed to low doses of virus, as well as the offspring of exposed individuals, are subsequently less susceptible to viral challenge. Relatively little is known about the mechanisms that underpin viral immunity but it is probable that the viral immune response is somewhat different to that of bacteria. We show that immune priming may, however, be a characteristic of both responses, mediated through different mechanisms, suggesting that immune memory may be a general phenomenon of insect immunity. This is important because immune priming may influence both host–parasite population and evolutionary dynamics.     

Multigenerational maternal effect on diapause induction in Trichogramma species (Hymenoptera: Trichogrammatidae)

Maternal photoperiodic response is known to influence the percentage of diapausing prepupae in Trichogramma species. However, the influence of several preceding generations has not yet been studied. We have investigated the stability of photoperiod-induced changes in multiple generations of Trichogramma buesi Voegele and Trichogramma principium Sug. et Sor. Short-day conditions during preimaginal development induced an increase in the percentage of diapausing progeny and grand progeny of both Trichogramma species. A similar trend was also detected in the fourth and fifth generations, but the response was weak although statistically significant. This grand-grandmaternal photoperiodic effect (which has not been demonstrated before for Trichogramma or for any other insect parasitoid) is most probably based on the transgenerational transmission of variations in DNA expression. We conclude that in mass rearing, to facilitate diapause induction before cold storage, it is advisable to rear both maternal and grandmaternal generations under the short-day conditions. In scientific studies, several generations preceding the experiment should be kept under equal conditions to exclude multigenerational maternal effects.     

Costs of resistance: genetic correlations and potential trade-offs in an insect immune system

Theory predicts that natural selection will erode additive genetic variation in fitness-related traits. However, numerous studies have found considerable heritable variation in traits related to immune function, which should be closely linked to fitness. This could be due to trade-offs maintaining variation in these traits. We used the Egyptian cotton leafworm, Spodoptera littoralis, as a model system to examine the quantitative genetics of insect immune function. We estimated the heritabilities of several different measures of innate immunity and the genetic correlations between these immune traits and a number of life history traits. Our results provide the first evidence for a potential genetic trade-off within the insect immune system, with antibacterial activity (lysozyme-like) exhibiting a significant negative genetic correlation with haemocyte density, which itself is positively genetically correlated with both haemolymph phenoloxidase activity and cuticular melanization. We speculate on a potential trade-off between defence against parasites and predators, mediated by larval colour, and its role in maintaining genetic variation in traits under natural selection.     

Translocation of bacteria from the gut to the eggs triggers maternal transgenerational immune priming in Tribolium castaneum

Invertebrates can be primed to enhance their protection against pathogens they have encountered before. This enhanced immunity can be passed maternally or paternally to the offspring and is known as transgenerational immune priming. We challenged larvae of the red flour beetle Tribolium castaneum by feeding them on diets supplemented with Escherichia coli, Micrococcus luteus or Pseudomonas entomophila, thus mimicking natural exposure to pathogens. The oral uptake of bacteria induced immunity-related genes in the offspring, but did not affect the methylation status of the egg DNA. However, we observed the translocation of bacteria or bacterial fragments from the gut to the developing eggs via the female reproductive system. Such translocating microbial elicitors are postulated to trigger bacterial strain-specific immune responses in the offspring and provide an alternative mechanistic explanation for maternal transgenerational immune priming in coleopteran insects.     

Integrating phylogenetic and ecological distances reveals new insights into parasite host specificity

The range of hosts a pathogen infects (host specificity) is a key element of disease risk that may be influenced by both shared phylogenetic history and shared ecological attributes of prospective hosts. Phylospecificity indices quantify host specificity in terms of host relatedness, but can fail to capture ecological attributes that increase susceptibility. For instance, similarity in habitat niche may expose phylogenetically unrelated host species to similar pathogen assemblages. Using a recently proposed method that integrates multiple distances, we assess the relative contributions of host phylogenetic and functional distances to pathogen host specificity (functional–phylogenetic host specificity). We apply this index to a data set of avian malaria parasite (Plasmodium and Haemoproteus spp.) infections from Melanesian birds to show that multihost parasites generally use hosts that are closely related, not hosts with similar habitat niches. We also show that host community phylogenetic ß‐diversity (Pßd) predicts parasite Pßd and that individual host species carry phylogenetically clustered Haemoproteus parasite assemblages. Our findings were robust to phylogenetic uncertainty, and suggest that phylogenetic ancestry of both hosts and parasites plays important roles in driving avian malaria host specificity and community assembly. However, restricting host specificity analyses to either recent or historical timescales identified notable exceptions, including a ‘habitat specialist’ parasite that infects a diversity of unrelated host species with similar habitat niches. This work highlights that integrating ecological and phylogenetic distances provides a powerful approach to better understand drivers of pathogen host specificity and community assembly.     

Thermal legacies: transgenerational effects of temperature on growth in a vertebrate

Transgenerational plasticity (TGP), a generalisation of more widely studied maternal effects, occurs whenever environmental cues experienced by either parent prior to fertilisation results in a modification of offspring reaction norms. Such effects have been observed in many traits across many species. Despite enormous potential importance-particularly in an era of rapid climate change-TGP in thermal growth physiology has never been demonstrated for vertebrates. We provide the first evidence for thermal TGP in a vertebrate: given sufficient time, sheepshead minnows adaptively program their offspring for maximal growth at the present temperature. The change in growth over a single generation (c. 30%) exceeds the single-generation rate of adaptive evolution by an order of magnitude. If widespread, transgenerational effects on thermal performance may have important implications on physiology, ecology and contemporary evolution, and may significantly alter the extinction risk posed by changing climate.     

Temperature and host diet jointly influence the outcome of infection in a Daphnia-fungal parasite system

1. Climate change has the potential to shape the future of infectious diseases, both directly and indirectly. In aquatic systems, for example, elevated temperatures can modulate the infectivity of waterborne parasites and affect the immune response of zooplanktonic hosts. Moreover, lake warming causes shifts in the communities of primary producers towards cyanobacterial dominance, thus lowering the quality of zooplankton diet. This may further affect host fitness, resulting in suboptimal resources available for parasite growth.
2. Previous experimental studies have demonstrated the respective effects of temperature and host diet on infection outcomes, using the zooplankter Daphnia and its microparasites as model systems. Although cyanobacteria blooms and heat waves are concurrent events in nature, few attempts have been made to combine both stressors in experimental settings.
3. Here, we raised the zooplankter Daphnia (two genotypes) under a full factorial design with varying levels of temperature (the standard 19°C and elevated 23°C), food quality (Scenedesmus obliquus as high-quality green algae, Microcystis aeruginosa and Planktothrix agardhii as low-quality cyanobacteria) and exposed them to the parasitic yeast Metschnikowia bicuspidata. We recorded life history parameters of the host as well as parasite traits related to transmission.
4. The combination of low-quality cyanobacterial diets and elevated temperature resulted in additive detrimental effects on host fecundity. Low-quality diets reduced parasite output, while temperature effects were context dependent. Overall, we argue that the combined effects of elevated water temperature and poor-quality diets may decrease epidemics of a common fungal parasite under a climate change scenario.

     

细菌耐药影响肠道菌群及其宿主免疫调控

抗生素在养殖业、医疗业及制药业的广泛应用导致环境中的细菌耐药性日益严重,环境中的抗生素及耐药细菌一旦进入人体肠道,将破坏肠道菌群稳态,对人体健康造成威胁,而残存于饮食中的环境污染物则加剧了细菌耐药造成的人体健康影响。文中在总结大量文献的基础上,阐述了细菌耐药对人体和动物肠道菌群的影响机制及其相关的机体免疫调控,以环境中影响人体肠道菌群获得耐药性的来源作为切入点,阐述抗生素和耐药细菌进入人体肠道后对人体肠道菌群结构和耐药基因组成的影响,以及与人体免疫和免疫调节相关疾病之间的相关机制,并对今后的研究方向进行了展望。     

Trans-generational immune priming is not mediated by the sex of the parent primed: a meta-analysis of invertebrate data

Traditionally, only vertebrates were thought capable of acquired immune responses, such as the ability to transfer immunological experience vertically to their offspring (known as trans-generational immune priming, TGIP). Increasing evidence challenges this belief and it is now clear that invertebrates also have the ability to exhibit functionally equivalent TGIP. This has led to a surge in papers exploring invertebrate TGIP, with most focusing on the costs, benefits or factors that affect the evolution of this trait. Whilst many studies have found support for the phenomenon, not all studies do, and there is considerable variation in the strength of positive results. To address this, we conducted a meta-analysis to answer the question: what is the overall effect of TGIP in invertebrates? Then, to understand the specific factors that affect its presence and intensity, we conducted a moderator analysis. Our results corroborate that TGIP occurs in invertebrates (demonstrated by a large, positive effect size). The strength of the positive effect was related to if and how offspring were immune challenged (i.e. whether they were challenged with the same or different insult as their parents or not challenged at all). Interestingly, there was no effect of the ecology or life history of the species or the sex of the parent or the offspring primed, and responses were comparable across different immune elicitors. Our publication bias testing suggests that the literature may suffer from some level of positive-result bias. However, even after accounting for potential bias, our effect size remains positive. Publication bias testing can be influenced by diversity in the data set, which was considerable in our data, even after moderator analysis. It is therefore conceivable that differences among studies could be caused by other moderators that were unable to be included in our meta-analysis. Nonetheless, our results suggest that TGIP does occur in invertebrates, whilst providing some potential avenues to examine the factors that account for variation in effect sizes.     

Coupling between tolerance and resistance for two related Eimeria parasite species

Resistance (host capacity to reduce parasite burden) and tolerance (host capacity to reduce impact on its health for a given parasite burden) manifest two different lines of defense. Tolerance can be independent from resistance, traded off against it, or the two can be positively correlated because of redundancy in underlying (immune) processes. We here tested whether this coupling between tolerance and resistance could differ upon infection with closely related parasite species. We tested this in experimental infections with two parasite species of the genus Eimeria. We measured proxies for resistance (the (inverse of) number of parasite transmission stages (oocysts) per gram of feces at the day of maximal shedding) and tolerance (the slope of maximum relative weight loss compared to day of infection on number of oocysts per gram of feces at the day of maximal shedding for each host strain) in four inbred mouse strains and four groups of F1 hybrids belonging to two mouse subspecies, Mus musculus domesticus and Mus musculus musculus. We found a negative correlation between resistance and tolerance against Eimeria falciformis, while the two are uncoupled against Eimeria ferrisi. We conclude that resistance and tolerance against the first parasite species might be traded off, but evolve more independently in different mouse genotypes against the latter. We argue that evolution of the host immune defenses can be studied largely irrespective of parasite isolates if resistance–tolerance coupling is absent or weak (E. ferrisi) but host–parasite coevolution is more likely observable and best studied in a system with negatively correlated tolerance and resistance (E. falciformis).     

The influences of host plant and genetic resistance to Bacillus thuringiensis on trade-offs between offspring number and growth rate in cabbage loopers, Trichoplusia ni

Abstract.  1. Variation in progeny size and quality is common among insects and this variation can strongly influence individual fitness. Larger progeny typically survive better and develop faster under adverse conditions and may have higher fecundity. Due to resource limitations, however, trade-offs may arise between having fewer large offspring or more smaller ones.
2. For cabbage loopers, Trichoplusia ni , pepper leaves are a poorer larval host than cucumber or tomato leaves as indicated by survival, development rate, and body size. Moths reared on cucumber produced more slower growing offspring than those that had been reared on pepper, which produced fewer, faster growing progeny.
3. Traits conferring resistance to Bacillus thuringiensis ( Bt ) generally are associated with strong deleterious effects that may influence resource allocation and reproductive trade-offs between progeny size and number.
4. Unlike the host-plant related trade-off between progeny size and fecundity observed among susceptible control moths, Bt -resistant parents had both the lowest fecundity and smallest progeny size on all host plants. This finding suggests that the progeny size–number relationship is constrained in resistant individuals.     

Challenges of metamorphosis in invertebrate hosts: maintaining parasite resistance across life‐history stages

1. Insects lack the acquired immune system of vertebrates, but there is some evidence that insect immunity can be primed against an encountered pathogen to mitigate the intensity of future infections within a life stage. 2. Many invertebrates have multiple life‐history stages separated by complete metamorphosis, but different life stages can often be infected by the same pathogens, and the potential loss of immune priming during metamorphosis could therefore have detrimental effects on the host. Evidence that invertebrate immune priming can persist through metamorphosis is still missing, and consequently it is unclear how host–parasite interactions change across different life‐history stages in the context of infection history. 3. By experimentally manipulating the infection history of the flour beetle Tribolium confusum, we show that intestinal gregarine parasite infections during the larval stage reduced parasite load in adults, demonstrating that a host‐controlled mechanism for parasite resistance can persist through complete metamorphosis in insects. 4. Infections reduced larval developmental rates and increased host mortality but only during the crucial metamorphic stage, indicating that parasites impact multiple life stages. In general, our results demonstrate that invertebrates can show surprisingly robust immune priming despite dramatic physiological changes and protect hosts across completely different life‐history stages.     

Variation in costs of parasite resistance among natural host populations

Organisms that can resist parasitic infection often have lower fitness in the absence of parasites. These costs of resistance can mediate host evolution during parasite epidemics. For example, large epidemics will select for increased host resistance. In contrast, small epidemics (or no disease) can select for increased host susceptibility when costly resistance allows more susceptible hosts to outcompete their resistant counterparts. Despite their importance for evolution in host populations, costs of resistance (which are also known as resistance trade‐offs) have mainly been examined in laboratory‐based host–parasite systems. Very few examples come from field‐collected hosts. Furthermore, little is known about how resistance trade‐offs vary across natural populations. We addressed these gaps using the freshwater crustacean Daphnia dentifera and its natural yeast parasite, Metschnikowia bicuspidata. We found a cost of resistance in two of the five populations we studied – those with the most genetic variation in resistance and the smallest epidemics in the previous year. However, yeast epidemics in the current year did not alter slopes of these trade‐offs before and after epidemics. In contrast, the no‐cost populations showed little variation in resistance, possibly because large yeast epidemics eroded that variation in the previous year. Consequently, our results demonstrate variation in costs of resistance in wild host populations. This variation has important implications for host evolution during epidemics in nature.     

Grandparental effects in marine sticklebacks: transgenerational plasticity across multiple generations

Nongenetic inheritance mechanisms such as transgenerational plasticity (TGP) can buffer populations against rapid environmental change such as ocean warming. Yet, little is known about how long these effects persist and whether they are cumulative over generations. Here, we tested for adaptive TGP in response to simulated ocean warming across parental and grandparental generations of marine sticklebacks. Grandparents were acclimated for two months during reproductive conditioning, whereas parents experienced developmental acclimation, allowing us to compare the fitness consequences of short‐term vs. prolonged exposure to elevated temperature across multiple generations. We found that reproductive output of F1 adults was primarily determined by maternal developmental temperature, but carry‐over effects from grandparental acclimation environments resulted in cumulative negative effects of elevated temperature on hatching success. In very early stages of growth, F2 offspring reached larger sizes in their respective paternal and grandparental environment down the paternal line, suggesting that other factors than just the paternal genome may be transferred between generations. In later growth stages, maternal and maternal granddam environments strongly influenced offspring body size, but in opposing directions, indicating that the mechanism(s) underlying the transfer of environmental information may have differed between acute and developmental acclimation experienced by the two generations. Taken together, our results suggest that the fitness consequences of parental and grandparental TGP are highly context dependent, but will play an important role in mediating some of the impacts of rapid climate change in this system.