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The germ theory states that pathogenic microorganisms are responsible for causing infectious diseases. The theory is inherently microbe-centric and does not account for variability in disease severity among individuals and asymptomatic carriership-two phenomena indicating an important role for host variability in infection outcome. The basic tenet of the germ theory was recently challenged, and a radically host-centric paradigm referred to as the "full-blown host theory" was proposed. According to this view, the pathogen is reduced to a passive environmental trigger, and the development of disease is instead due to pre-existing immunodeficiencies of the host. Here, we consider the factors that determine disease severity using established knowledge concerning evolutionary biology, microbial pathogenesis, and host-pathogen interactions. We note that the available data support a noncentric view that recognizes key roles for both the causative microbe and the host in dictating infection outcome.
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Teoría del Gérmen de la Enfermedad , Interacciones Huésped-Patógeno , HumanosRESUMEN
Variability in disease severity caused by a microbial pathogen is impacted by each infection representing a unique combination of host and pathogen genomes. Here, we show that the outcome of invasive Streptococcus pyogenes infection is regulated by an interplay between human STING genotype and bacterial NADase activity. S. pyogenes-derived c-di-AMP diffuses via streptolysin O pores into macrophages where it activates STING and the ensuing type I IFN response. However, the enzymatic activity of the NADase variants expressed by invasive strains suppresses STING-mediated type I IFN production. Analysis of patients with necrotizing S. pyogenes soft tissue infection indicates that a STING genotype associated with reduced c-di-AMP-binding capacity combined with high bacterial NADase activity promotes a 'perfect storm' manifested in poor outcome, whereas proficient and uninhibited STING-mediated type I IFN production correlates with protection against host-detrimental inflammation. These results reveal an immune-regulating function for bacterial NADase and provide insight regarding the host-pathogen genotype interplay underlying invasive infection and interindividual disease variability.
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NAD+ Nucleosidasa , Streptococcus pyogenes , Humanos , Proteínas Bacterianas/genética , Genotipo , Macrófagos/microbiología , NAD+ Nucleosidasa/genética , Streptococcus pyogenes/genéticaRESUMEN
BACKGROUND: Selection pressure exerted by pathogens can influence patterns of genetic diversity in the host. In the immune system especially, numerous genes encode proteins involved in antagonistic interactions with pathogens, paving the way for coevolution that results in increased genetic diversity as a consequence of balancing selection. The complement system is a key component of innate immunity. Many complement proteins interact directly with pathogens, either by recognising pathogen molecules for complement activation, or by serving as targets of pathogen immune evasion mechanisms. Complement genes can therefore be expected to be important targets of pathogen-mediated balancing selection, but analyses of such selection on this part of the immune system have been limited. RESULTS: Using a population sample of whole-genome resequencing data from wild bank voles (n = 31), we estimated the extent of genetic diversity and tested for signatures of balancing selection in multiple complement genes (n = 44). Complement genes showed higher values of standardised ß (a statistic expected to be high under balancing selection) than the genome-wide average of protein coding genes. One complement gene, FCNA, a pattern recognition molecule that interacts directly with pathogens, was found to have a signature of balancing selection, as indicated by the Hudson-Kreitman-Aguadé test (HKA) test. Scans for localised signatures of balancing selection in this gene indicated that the target of balancing selection was found in exonic regions involved in ligand binding. CONCLUSION: The present study adds to the growing evidence that balancing selection may be an important evolutionary force on components of the innate immune system. The identified target in the complement system typifies the expectation that balancing selection acts on genes encoding proteins involved in direct interactions with pathogens.
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Proteínas del Sistema Complemento , Selección Genética , Análisis de Secuencia de ADN , Proteínas del Sistema Complemento/genéticaRESUMEN
Antagonistic coevolution (i.e., reciprocal adaptation and counter-adaptation) between hosts and pathogens has long been considered an important driver of genetic variation. However, direct evidence for this is still scarce, especially in vertebrates. The wealth of data on genetics of susceptibility to infectious disease in humans provides an important resource for understanding host-pathogen coevolution, but studies of humans are rarely framed in coevolutionary theory. Here, I review data from human host-pathogen systems to critically assess the evidence for a key assumption of models of host-pathogen coevolution-the presence of host genotype-by-pathogen genotype interactions (G×G). I also attempt to infer whether observed G×G fit best with "gene-for-gene" or "matching allele" models of coevolution. I find that there are several examples of G×G in humans (involving, e.g., ABO, HBB, FUT2, SLC11A1, and HLA genes) that fit assumptions of either gene-for-gene or matching allele models. This means that there is potential for coevolution to drive polymorphism also in humans (and presumably other vertebrates), but further studies are required to investigate how widespread this process is.
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Adaptación Fisiológica , Evolución Biológica , Animales , Humanos , Genotipo , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-ParásitosRESUMEN
MHC genes are extraordinarily polymorphic in most taxa. Host-pathogen coevolution driven by negative frequency-dependent selection (NFDS) is one of the main hypotheses for the maintenance of such immunogenetic variation. Here, we test a critical but rarely tested assumption of this hypothesis-that MHC alleles affect resistance/susceptibility to a pathogen in a strain-specific way, that is, there is a host genotype-by-pathogen genotype interaction. In a field study of bank voles naturally infected with the tick-transmitted bacterium Borrelia afzelii, we tested for MHC class II (DQB) genotype-by-B. afzelii strain interactions for infection prevalence between 10 DQB alleles and seven strains. One allele (DQB*37) showed an interaction, such that voles carrying DQB*37 had higher prevalence of two strains and lower prevalence of one strain than individuals without the allele. These findings were corroborated by analyses of strain composition of infections, which revealed an effect of DQB*37 in the form of lower ß diversity among infections in voles carrying the allele. Taken together, these results provide rare support at the molecular genetic level for a key assumption of models of antagonistic coevolution through NFDS.
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Borrelia , Animales , Arvicolinae/genética , Genotipo , Prevalencia , RoedoresRESUMEN
BACKGROUND: Hosts are often simultaneously infected with several parasite species. These co-infections can lead to within-host interactions of parasites, including mutualism and competition, which may affect both virulence and transmission. Birds are frequently co-infected with different haemosporidian parasites, but very little is known about if and how these parasites interact in natural host populations and what consequences there are for the infected hosts. We therefore set out to study Plasmodium and Haemoproteus parasites in house sparrows Passer domesticus with naturally acquired infections using a protocol where the parasitemia (infection intensity) is quantified by qPCR separately for the two parasites. We analysed infection status (presence/absence of the parasite) and parasitemia of parasites in the blood of both adult and juvenile house sparrows repeatedly over the season. RESULTS: Haemoproteus passeris and Plasmodium relictum were the two dominating parasite species, found in 99% of the analyzed Sanger sequences. All birds were infected with both Plasmodium and Haemoproteus parasites during the study period. Seasonality explained infection status for both parasites in the adults: H. passeris was completely absent in the winter while P. relictum was present all year round. Among adults infected with H. passeris there was a positive effect of P. relictum parasitemia on H. passeris parasitemia and likewise among adults infected with P. relictum there was a positive effect of H. passeris parasitemia on P. relictum parasitemia. No such associations on parasitemia were seen in juvenile house sparrows. CONCLUSIONS: The reciprocal positive relationships in parasitemia between P. relictum and H. passeris in adult house sparrows suggests either mutualistic interactions between these frequently occurring parasites or that there is variation in immune responses among house sparrow individuals, hence some individuals suppress the parasitemia of both parasites whereas other individuals suppress neither. Our detailed screening of haemosporidian parasites over the season shows that co-infections are very frequent in both juvenile and adult house sparrows, and since co-infections often have stronger negative effects on host fitness than the single infection, it is imperative to use screening systems with the ability to detect multiple parasites in ecological studies of host-parasite interactions.
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Coinfección , Haemosporida , Malaria Aviar , Parásitos , Plasmodium , Gorriones , Animales , Coinfección/epidemiología , Humanos , Malaria Aviar/epidemiología , Parasitemia/veterinaria , Gorriones/parasitologíaRESUMEN
The high polymorphism of Major Histocompatibility Complex (MHC) genes is generally considered to be a result of pathogen-mediated balancing selection. Such selection may operate in the form of heterozygote advantage, and/or through specific MHC allele-pathogen interactions. Specific MHC allele-pathogen interactions may promote polymorphism via negative frequency-dependent selection (NFDS), or selection that varies in time and/or space because of variability in the composition of the pathogen community (fluctuating selection; FS). In addition, divergent allele advantage (DAA) may act on top of these forms of balancing selection, explaining the high sequence divergence between MHC alleles. DAA has primarily been thought of as an extension of heterozygote advantage. However, DAA could also work in concert with NFDS though this is yet to be tested explicitly. To evaluate the importance of DAA in pathogen-mediated balancing selection, we surveyed allelic polymorphism of MHC class II DQB genes in wild bank voles (Myodes glareolus) and tested for associations between DQB haplotypes and infection by Borrelia afzelii, a tick-transmitted bacterium causing Lyme disease in humans. We found two significant associations between DQB haplotypes and infection status: one haplotype was associated with lower risk of infection (resistance), while another was associated with higher risk of infection (susceptibility). Interestingly, allelic divergence within individuals was higher for voles with the resistance haplotype compared to other voles. In contrast, allelic divergence was lower for voles with the susceptibility haplotype than other voles. The pattern of higher allelic divergence in individuals with the resistance haplotype is consistent with NFDS favouring divergent alleles in a natural population, hence selection where DAA works in concert with NFDS.
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Arvicolinae , Grupo Borrelia Burgdorferi/inmunología , Haplotipos , Antígenos de Histocompatibilidad Clase II , Enfermedad de Lyme , Polimorfismo Genético , Animales , Arvicolinae/genética , Arvicolinae/inmunología , Arvicolinae/microbiología , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase II/inmunología , Enfermedad de Lyme/genética , Enfermedad de Lyme/inmunologíaRESUMEN
The tick-transmitted bacterium Borrelia afzelii consists of a number of antigenically different strains - often defined by outer surface protein C (OspC) genotype - that coexist at stable frequencies in host populations. To investigate how host antibody responses affect strain coexistence, we measured antibody cross-reactivity to three different OspC types (OspC 2, 3 and 9) in three different strains of laboratory mice (BALB/c, C3H and C57BL/6). The extent of cross-reactivity differed between mouse strains, being higher in C3H than BALB/c and C57BL/6. In one of three pairwise comparisons of OspC types (OspC2 vs OspC9), there was evidence for asymmetry of cross-reactivity, with antibodies to OspC2 cross-reacting more strongly with OspC9 than vice versa. These results indicate that the extent of antibody-mediated competition between OspC types may depend on the composition of the host population, and that such competition may be asymmetric. We discuss the implications of these results for understanding the coexistence of OspC types.
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Anticuerpos Antibacterianos/inmunología , Antígenos Bacterianos/inmunología , Proteínas de la Membrana Bacteriana Externa/inmunología , Grupo Borrelia Burgdorferi/inmunología , Animales , Reacciones Cruzadas , Femenino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratones Endogámicos C57BLRESUMEN
Differences in immune function between species could be a result of interspecific divergence in coding sequence and/or expression of immune genes. Here, we investigate how the degree of divergence in coding sequence and expression differs between functional categories of immune genes, and if differences between categories occur independently of other factors (expression level, pleiotropy). To this end, we compared spleen transcriptomes of wild-caught yellow-necked mice and bank voles. Immune genes expressed in the spleen were divided into four categories depending on the function of the encoded protein: pattern recognition receptors (PRR); signal transduction proteins; transcription factors; and cyto- and chemokines and their receptors. Genes encoding PRR and cyto-/chemokines had higher sequence divergence than genes encoding signal transduction proteins and transcription factors, even when controlling for potentially confounding factors. Genes encoding PRR also had higher expression divergence than genes encoding signal transduction proteins and transcription factors. There was a positive correlation between expression divergence and coding sequence divergence, in particular for PRR genes. We propose that this is a result of that divergence in PRR coding sequence leads to divergence in PRR expression through positive feedback of PRR ligand binding on PRR expression. When controlling for sequence divergence, expression divergence of PRR genes did not differ from other categories. Taken together, the results indicate that coding sequence divergence of PRR genes is a major cause of differences in immune function between species.
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Murinae/genética , Murinae/inmunología , Animales , Arvicolinae/genética , Quimiocinas , Evolución Molecular , Expresión Génica , Pleiotropía Genética , Ratones , Receptores de Reconocimiento de Patrones/genética , TranscriptomaRESUMEN
Different host species often differ considerably in susceptibility to a given pathogen, but the causes of such differences are rarely known. The natural hosts of the tick-transmitted bacterium Borrelia afzelii, which is one of causative agents of Lyme borreliosis in humans, include a variety of small mammals like voles and mice. Previous studies have shown that B. afzelii-infected bank voles (Myodes glareolus) have about ten times higher bacterial load than infected yellow-necked mice (Apodemus flavicollis), indicating that these two species differ in resistance. In this study, we compared the immune response to B. afzelii infection in these host species by using RNA sequencing to quantify gene expression in spleen. Gene set enrichment analysis (GSEA) showed that several immune pathways were down-regulated in infected animals in both bank voles and yellow-necked mice. Moreover, IFNα response was up-regulated in B. afzelii-infected yellow-necked mice, while IL6 signaling and the complement pathway were down-regulated in infected bank voles; differences in regulation of these three pathways between bank voles and yellow-necked mice could thus contribute to the difference in resistance to B. afzelii between the species. This study provides knowledge of gene expression induced by a zoonotic pathogen in its natural host, and possible species-specific regulation of immune responses associated with resistance.
RESUMEN
Pathogen-mediated balancing selection is commonly considered to play an important role in the maintenance of genetic diversity, in particular in immune genes. However, the factors that may influence which immune genes are the targets of such selection are largely unknown. To address this, here we focus on Pattern Recognition Receptor (PRR) signalling pathways, which play a key role in innate immunity. We used whole-genome resequencing data from a population of bank voles (Myodes glareolus) to test for associations between balancing selection, pleiotropy and gene function in a set of 123 PRR signalling pathway genes. To investigate the effect of gene function, we compared genes encoding (a) receptors for microbial ligands versus downstream signalling proteins, and (b) receptors recognizing components of microbial cell walls, flagella and capsids versus receptors recognizing features of microbial nucleic acids. Analyses based on the nucleotide diversity of full coding sequences showed that balancing selection primarily targeted receptor genes with a low degree of pleiotropy. Moreover, genes encoding receptors recognizing components of microbial cell walls etc. were more important targets of balancing selection than receptors recognizing nucleic acids. Tests for localized signatures of balancing selection in coding and noncoding sequences showed that such signatures were mostly located in introns, and more evenly distributed among different functional categories of PRR pathway genes. The finding that signatures of balancing selection in full coding sequences primarily occur in receptor genes, in particular those encoding receptors for components of microbial cell walls etc., is consistent with the idea that coevolution between hosts and pathogens is an important cause of balancing selection on immune genes.
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Arvicolinae/genética , Evolución Molecular , Pleiotropía Genética , Inmunidad Innata , Receptores de Reconocimiento de Patrones/genética , Selección Genética , AnimalesRESUMEN
Key topics in the study of host-microbe interactions-such as the prevention of drug resistance and the exploitation of beneficial effects of bacteria-would benefit from concerted efforts with both mechanistic and evolutionary approaches. But due to differences in intellectual traditions, insights gained in one field rarely benefit the other. Here, we develop a conceptual and analytical framework for the integrated study of host-microbe interactions. This framework partitions the health effects of microbes and the effector molecules they produce into components with different evolutionary implications. It thereby facilitates the prediction of evolutionary responses to inhibition and exploitation of specific molecular mechanisms.
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Studies of Borrelia burgdorferi sensu lato in laboratory mice and humans have shown that spirochaetes disseminate from the site of infection (skin) to internal tissues, and cause various pathological effects. However, less is known about colonization and pathology of Lyme borreliosis spirochaetes in their natural hosts. In the present study, we assessed the colonization and manifestations during B. afzelii infection in reservoir hosts (yellow-necked mouse, Apodemus flavicollis; bank vole, Myodes glareolus; common shrew, Sorex araneus) infected in the wild. The infection prevalence and bacterial load was measured in skin (ear), joints and heart by quantitative PCR, and pathology in infected joints was evaluated by histology. The prevalence of B. afzelii was higher in skin than in joints and heart, but most animals that were positive in skin were also positive in internal tissues, and there was no difference between species in tissue-specific prevalence. Thus, spirochaetes disseminated from skin to other tissues in a similar way in all species. The bacterial load varied among host species and among different tissues within the same host species. In the case of skin and joints, bank voles and common shrews had higher bacterial loads than yellow-necked mice. In hearts, voles had higher bacterial loads than shrews and mice. Histological analyses showed no inflammation in joints of infected animals when compared to controls. We conclude that B. afzelii disseminates to internal tissues in natural hosts, but that levels of colonization vary between both species and tissues. There is as yet little evidence for pathological effects in natural hosts.
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Grupo Borrelia Burgdorferi/patogenicidad , Borrelia burgdorferi/patogenicidad , Reservorios de Enfermedades/microbiología , Enfermedad de Lyme/patología , Enfermedad de Lyme/veterinaria , Animales , Arvicolinae/microbiología , Carga Bacteriana , Borrelia burgdorferi/genética , Grupo Borrelia Burgdorferi/genética , Ixodes/microbiología , Murinae/microbiología , Prevalencia , Reacción en Cadena en Tiempo Real de la Polimerasa , Estaciones del Año , Musarañas/microbiología , Infestaciones por Garrapatas/microbiología , Infestaciones por Garrapatas/veterinaria , Tropismo ViralRESUMEN
Studies of infection by Phytophthora infestans-the causal agent of potato late blight-in wild species can provide novel insights into plant defense responses, and indicate how wild plants might be influenced by recurrent epidemics in agricultural fields. In the present study, our aim was to investigate if different clones of Solanum dulcamara (a relative of potato) collected in the wild differ in resistance and tolerance to infection by a common European isolate of P. infestans. We performed infection experiments with six S. dulcamara genotypes (clones) both in the laboratory and in the field and measured the degree of infection and plant performance traits. In the laboratory, the six evaluated genotypes varied from resistant to susceptible, as measured by degree of infection 20 days post infection. Two of the four genotypes susceptible to infection showed a quadratic (concave downward) relationship between the degree of infection and shoot length, with maximum shoot length at intermediate values of infection. This result suggests overcompensation, that is, an increase in growth in infected individuals. The number of leaves decreased with increasing degree of infection, but at different rates in the four susceptible genotypes, indicating genetic variation for tolerance. In the field, the inoculated genotypes did not show any disease symptoms, but plant biomass at the end of the growing season was higher for inoculated plants than for controls, in-line with the overcompensation detected in the laboratory. We conclude that in S. dulcamara there are indications of genetic variation for both resistance and tolerance to P. infestans infection. Moreover, some genotypes displayed overcompensation. Learning about plant tolerance and overcompensation to infection by pathogens can help broaden our understanding of plant defense in natural populations and help develop more sustainable plant protection strategies for economically important crop diseases.
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BACKGROUND: The Major Histocompatibility Complex (MHC) plays a central role in immunity and has been given considerable attention by evolutionary ecologists due to its associations with fitness-related traits. Songbirds have unusually high numbers of MHC class I (MHC-I) genes, but it is not known whether all are expressed and equally important for immune function. Classical MHC-I genes are highly expressed, polymorphic and present peptides to T-cells whereas non-classical MHC-I genes have lower expression, are more monomorphic and do not present peptides to T-cells. To get a better understanding of the highly duplicated MHC genes in songbirds, we studied gene expression in a phylogenetic framework in three species of sparrows (house sparrow, tree sparrow and Spanish sparrow), using high-throughput sequencing. We hypothesize that sparrows could have classical and non-classical genes, as previously indicated though never tested using gene expression. RESULTS: The phylogenetic analyses reveal two distinct types of MHC-I alleles among the three sparrow species, one with high and one with low level of polymorphism, thus resembling classical and non-classical genes, respectively. All individuals had both types of alleles, but there was copy number variation both within and among the sparrow species. However, the number of highly polymorphic alleles that were expressed did not vary between species, suggesting that the structural genomic variation is counterbalanced by conserved gene expression. Overall, 50% of the MHC-I alleles were expressed in sparrows. Expression of the highly polymorphic alleles was very variable, whereas the alleles with low polymorphism had uniformly low expression. Interestingly, within an individual only one or two alleles from the polymorphic genes were highly expressed, indicating that only a single copy of these is highly expressed. CONCLUSIONS: Taken together, the phylogenetic reconstruction and the analyses of expression suggest that sparrows have both classical and non-classical MHC-I genes, and that the evolutionary origin of these genes predate the split of the three investigated sparrow species 7 million years ago. Because only the classical MHC-I genes are involved in antigen presentation, the function of different MHC-I genes should be considered in future ecological and evolutionary studies of MHC-I in sparrows and other songbirds.
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Genes MHC Clase I , Gorriones/clasificación , Gorriones/genética , Animales , Evolución Biológica , Variaciones en el Número de Copia de ADN , Evolución Molecular , Expresión Génica , FilogeniaRESUMEN
Infection tolerance is the ability of a host to limit the health effects of a given parasite load. A few recent studies have demonstrated genetic variation for tolerance, but little is known about how environmental factors affect tolerance. Here, we used the intestinal nematode Heligmosomoides polygyrus in laboratory mice to test for effects of protein malnutrition on tolerance. We performed an experiment where two different mouse strains (CBA and BALB/c) were fed either adequate-protein food or low-protein food, and trickle-infected with different doses of H. polygyrus larvae during four weeks. We found that protein malnutrition decreases tolerance measured as intestinal barrier function, but only in one of the strains (BALB/c); that is, there was a host genotype-by-environment interaction for tolerance. We conclude that nutritional status can affect tolerance and that sensitivity of tolerance to malnutrition may differ between host genotypes.
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Parasitosis Intestinales/parasitología , Nematospiroides dubius/fisiología , Deficiencia de Proteína/parasitología , Infecciones por Strongylida/parasitología , Animales , Proteínas en la Dieta , Resistencia a la Enfermedad/genética , Variación Genética , Interacciones Huésped-Parásitos , Tolerancia Inmunológica , Parasitosis Intestinales/inmunología , Mucosa Intestinal/inmunología , Mucosa Intestinal/parasitología , Ratones Endogámicos BALB C , Ratones Endogámicos CBA , Deficiencia de Proteína/inmunología , Infecciones por Strongylida/inmunologíaRESUMEN
Infections frequently consist of more than one strain of a given pathogen. Experiments have shown that co-infecting strains often compete, so that the infection intensity of each strain in mixed infections is lower than in single strain infections. Such within-host competition can have important epidemiological and evolutionary consequences. However, the extent of competition has rarely been investigated in wild, naturally infected hosts, where there is noise in the form of varying inoculation doses, asynchronous infections and host heterogeneity, which can potentially alleviate or eliminate competition. Here, we investigated the extent of competition between Borrelia afzelii strains (as determined by ospC genotype) in three host species sampled in the wild. For this purpose, we developed a protocol for 454 amplicon sequencing of ospC, which allows both detection and quantification of each individual strain in an infection. Each host individual was infected with one to six ospC strains. The infection intensity of each strain was lower in mixed infections than in single ones, showing that there was competition. Rank-abundance plots revealed that there was typically one dominant strain, but that the evenness of the relative infection intensity of the different strains in an infection increased with the multiplicity of infection. We conclude that within-host competition can play an important role under natural conditions despite many potential sources of noise, and that quantification by next-generation amplicon sequencing offers new possibilities to dissect within-host interactions in naturally infected hosts.
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Antígenos Bacterianos/genética , Proteínas de la Membrana Bacteriana Externa/genética , Grupo Borrelia Burgdorferi/genética , Grupo Borrelia Burgdorferi/patogenicidad , Animales , Arvicolinae/microbiología , ADN Bacteriano/genética , Genes Bacterianos , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Especificidad del Huésped , Interacciones Huésped-Patógeno/genética , Enfermedad de Lyme/microbiología , Enfermedad de Lyme/veterinaria , Murinae/microbiología , Análisis de Secuencia de ADN , Musarañas/virologíaRESUMEN
How do we defend ourselves against pathogenic microbes and other parasites infecting us? Research on defence against parasites has traditionally focused on resistance--the ability to prevent infection or limit parasite replication. The genetics, physiology, and evolutionary ecology of such traits are now relatively well understood. During the last few years it has been realized that another, conceptually different type of defence also plays an important role in animal host-parasite interactions. This type of defence is called tolerance, and can be defined as the ability to limit the health effects of parasites without preventing infection or controlling parasite replication. Our understanding of the causes and consequences of variation in tolerance is, however, still rudimentary. Three recent studies shed light on these questions. In a study of HIV in humans, Regoes et al. show that an MHC class I gene affects not only resistance (as previously known) but also tolerance. In a study of voles, Jackson et al. identify a transcription factor mediating age differences in tolerance to macroparasites. Finally, Hayward et al. demonstrate that tolerance to intestinal parasites in sheep is under positive directional selection, but that most of the variation is environmentally induced rather than heritable. These studies increase our knowledge of the genetic and physiological sources of variation in tolerance, and how this variation affects Darwinian fitness. In addition, they illustrate different approaches to untangle tolerance from other factors determining the health effects of infectious disease.
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Enfermedades Transmisibles , Interacciones Huésped-Parásitos , Animales , HumanosRESUMEN
Host specificity is a fundamental property of parasites. Whereas most studies focus on measures of specificity on host range, only few studies have considered quantitative aspects such as infection intensity or prevalence. The relative importance of these quantitative aspects is still unclear, mainly because of methodological constraints, yet central to a precise assessment of host specificity. Here, we assessed simultaneously two quantitative measures of host specificity of Heligmosomoides glareoli and Heligmosomoides polygyrus polygyrus infections in sympatric rodent hosts. We used standard morphological techniques as well as real-time quantitative PCR and sequencing of the rDNA ITS2 fragment to analyse parasite infection via faecal sample remains. Although both parasite species are thought to be strictly species-specific, we found morphologically and molecularly validated co- and cross-infections. We also detected contrasting patterns within and between host species with regard to specificity for prevalence and intensity of infection. H. glareoli intensities were twofold higher in bank voles than in yellow-necked mice, but prevalence did not differ significantly between species (33 vs. 18%). We found the opposite pattern in H. polygyrus infections with similar intensity levels between host species but significantly higher prevalence in mouse hosts (56 vs. 10%). Detection rates were higher with molecular tools than morphological methods. Our results emphasize the necessity to consider quantitative aspects of specificity for a full view of a parasites' capacity to replicate and transmit in hosts and present a worked example of how modern molecular tools help to advance our understanding of selective forces in host-parasite ecology and evolution.