| 1. |
- Råberg, Lars, et al.
(författare)
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MHC class II genotype-by-pathogen genotype interaction for infection prevalence in a natural rodent-Borrelia system
- 2022
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Ingår i: Evolution. - : Wiley. - 0014-3820 .- 1558-5646. ; 76:9, s. 2067-2075
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Tidskriftsartikel (refereegranskat)abstract
- 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 β 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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| 2. |
- Scherman, Kristin
(författare)
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MHC polymorphism and host-pathogen interactions: The case of Borrelia in its reservoir host, the bank vole Myodes glareolus
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The major histocompatibility complex (MHC) class IIB genes exhibit extensive allelic polymorphism, most likely maintained by pathogen-mediated balancing selection (PMBS). PMBS may operate in the form of heterozygote advantage (HA), and/or through the interaction of pathogens and specific MHC alleles via fluctuating selection (FS) or negative frequency-dependent selection (NFDS). In particular, NFDS is one of the primary models used to explain the extraordinary number of alleles found in the MHC genes. However, there is as yet limited empirical evidence for this hypothesis. Here, I use the tick-borne bacterium Borrelia afzelii in bank voles as a model system to study the maintenance of MHC class IIB variation for resistance to infectious diseases. I analyse both infection prevalence and infection intensity of Borrelia in a large-scale mark-recapture study (>500 bank voles). The prevalence and incidence of infection was higher in adults than immatures and peaked during the summer. Infection intensities decreased over time within individuals, and the loss of infection was significantly higher than the diagnostic error rate, in particular during winter, suggesting that bank voles can clear B. afzelii infections. I examined the rate ratio of replacement to silent amino acid substitutions in the peptide-binding region of the polymorphic MHC class II DRB and DQB genes in bank voles. I found signs of positive selection in both genes, but maximum likelihood models detected at least twice as many positively selected sites in DQB as in DRB, suggesting that DQB has been under stronger positive selection than DRB over evolutionary time. For this reason, I focused on DQB in my analyses of bank vole resistance to Borrelia. I analysed the effect of DQB-genotypes on both B. afzelii prevalence and strain-specific infection intensity. I tested 12 different DQB haplotypes for associations with infection prevalence. I found no evidence for HA in regards to B. afzelii prevalence. However, I found two significant associations between DQB haplotypes and infection prevalence: One haplotype was associated with resistance, while another was associated with susceptibility. The DQB intra-genotypic divergence was higher for voles with the resistance haplotype and lower in voles with the susceptible haplotype, compared to other voles. According to the divergent allele advantage hypothesis (DAA), individuals with a minimal overlap in antigen recognition of MHC-molecules should be selected for. I suggest that higher divergence in voles with resistance haplotypes (alleles), is consistent with selection where NFDS works in concert with DAA. The key assumption of NFDS is that there is a host-pathogen G×G for resistance to infection. To investigate if there is G×G between DQB and B. afzelii in bank voles, I analysed DQB haplotypes and infection intensity per B. afzelii strain. I found that one DQB haplotype had strain specific effects on quantitative resistance: Voles with haplotype H06 had lower infection intensities than voles without H06, with regards to some strains of B. afzelii. However, bank voles carrying the H06 haplotype had higher infection intensities of some other B.afzelii strains. This significant interaction between host MHC class II DQB haplotype and B. afzelii strains shows that there is potential for NFDS to maintain MHC allelic richness in a natural population of bank voles.
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| 3. |
- Andersson, Martin, et al.
(författare)
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Infection dynamics of the tick-borne pathogen 'Candidatus Neoehrlichia mikurensis' and co-infections with Borrelia afzelii in bank voles in Southern Sweden.
- 2014
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Ingår i: Applied and Environmental Microbiology. - 0099-2240. ; 80:5, s. 1645-1649
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Tidskriftsartikel (refereegranskat)abstract
- The tick-borne bacterium 'Candidatus Neoehrlichia mikurensis' has recently been recognized as a human pathogen. Together with Borrelia afzelii, it is one of the most common pathogens found in the tick Ixodes ricinus. Here, we compared the epidemiology of 'Candidatus N. mikurensis' and B. afzelii by longitudinal sampling from May to September in one of their most abundant vertebrate hosts, the bank vole (Myodes glareolus), using real-time PCR for detection and quantification. The prevalence of 'Candidatus N. mikurensis' and B. afzelii was 19% (50/261) and 22% (56/261), respectively. The prevalence of 'Candidatus N. mikurensis' increased significantly during the sampling season. The clearance rate of 'Candidatus N. mikurensis' was significantly higher than that of B. afzelii. We found a high frequency of double infections; 46% of all samples infected with 'Candidatus N. mikurensis' also had a co-infection with B. afzelii. The frequency of co-infections was significantly higher than expected from the prevalence of each pathogen. The high level of co-infections can be caused by interactions between the pathogens or might reflect variation in general susceptibility among voles.
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| 4. |
- Scherman, Kristin, et al.
(författare)
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Positive Selection on MHC Class II DRB and DQB Genes in the Bank Vole (Myodes glareolus).
- 2014
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Ingår i: Journal of Molecular Evolution. - : Springer Science and Business Media LLC. - 0022-2844 .- 1432-1432. ; 78:5, s. 293-305
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Tidskriftsartikel (refereegranskat)abstract
- The major histocompatibility complex (MHC) class IIB genes show considerable sequence similarity between loci. The MHC class II DQB and DRB genes are known to exhibit a high level of polymorphism, most likely maintained by parasite-mediated selection. Studies of the MHC in wild rodents have focused on DRB, whilst DQB has been given much less attention. Here, we characterised DQB genes in Swedish bank voles Myodes glareolus, using full-length transcripts. We then designed primers that specifically amplify exon 2 from DRB (202 bp) and DQB (205 bp) and investigated molecular signatures of natural selection on DRB and DQB alleles. The presence of two separate gene clusters was confirmed using BLASTN and phylogenetic analysis, where our seven transcripts clustered according to either DQB or DRB homologues. These gene clusters were again confirmed on exon 2 data from 454-amplicon sequencing. Our DRB primers amplify a similar number of alleles per individual as previously published DRB primers, though our reads are longer. Traditional d N/d S analyses of DRB sequences in the bank vole have not found a conclusive signal of positive selection. Using a more advanced substitution model (the Kumar method) we found positive selection in the peptide binding region (PBR) of both DRB and DQB genes. Maximum likelihood models of codon substitutions detected positively selected sites located in the PBR of both DQB and DRB. Interestingly, these analyses detected at least twice as many positively selected sites in DQB than DRB, suggesting that DQB has been under stronger positive selection than DRB over evolutionary time.
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| 5. |
- Andersson, Martin, et al.
(författare)
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Multiple-Strain Infections of Borrelia afzelii: A Role for Within-Host Interactions in the Maintenance of Antigenic Diversity?
- 2013
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Ingår i: American Naturalist. - : University of Chicago Press. - 0003-0147 .- 1537-5323. ; 181:4, s. 545-554
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Tidskriftsartikel (refereegranskat)abstract
- Genetically diverse infections are common but little is known about what effects coinfecting strains have on each other in natural host-parasite systems. To explore the nature and consequences of interactions in the wild, we studied the tick-transmitted bacterium Borrelia afzelii in one of its main reservoir hosts, the bank vole Myodes glareolus. We measured overall infection intensity with quantitative polymerase chain reaction (PCR) and resolved the composition of multiple infections using strain-specific PCR assays targeting the ospC gene (which encodes an immunodominant surface protein). We found seven different strains, as defined by ospC genotype. There was little evidence for interactions affecting infection intensities, but strains were highly aggregated (i.e., there were more multiple infections than expected from random co-occurrence). Moreover, there was a positive correlation between the difference at the amino acid level between two OspC types and their degree of association. Overall, the observed patterns suggest that facilitation is more important than competition in this system and that more diverse infections have an advantage in establishing and/or maintaining infection. We propose that this advantage is one of the factors that favors antigenic diversity.
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| 6. |
- Tschirren, Barbara, et al.
(författare)
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Polymorphisms at the innate immune receptor TLR2 are associated with Borrelia infection in a wild rodent population
- 2013
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Ingår i: Royal Society of London. Proceedings B. Biological Sciences. - : The Royal Society. - 1471-2954. ; 280:1759
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of the key role of Toll-like receptors (TLRs) in initiating innate immune responses and modulating adaptive immunity has revolutionized our understanding of vertebrate defence against pathogens. Yet, despite their central role in pathogen recognition and defence initiation, there is little information on how variation in TLRs influences disease susceptibility in natural populations. Here, we assessed the extent of naturally occurring polymorphisms at TLR2 in wild bank voles (Myodes glareolus) and tested for associations between TLR2 variants and infection with Borrelia afzelii, a common tick-transmitted pathogen in rodents and one of the causative agents of human Lyme disease. Bank voles in our population had 15 different TLR2 haplotypes (10 different haplotypes at the amino acid level), which grouped in three well-separated clusters. In a large-scale capture-mark-recapture study, we show that voles carrying TLR2 haplotypes of one particular cluster (TLR2(c2)) were almost three times less likely to be Borrelia infected than animals carrying other haplotypes. Moreover, neutrality tests suggested that TLR2 has been under positive selection. This is, to our knowledge, the first demonstration of an association between TLR polymorphism and parasitism in wildlife, and a striking example that genetic variation at innate immune receptors can have a large impact on host resistance.
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| 7. |
- Tschirren, Barbara, et al.
(författare)
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Contrasting patterns of diversity and population differentiation at the innate immunity gene toll-like receptor 2 (tlr2) in two sympatric rodent species.
- 2012
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Ingår i: Evolution. - : Wiley. - 1558-5646 .- 0014-3820. ; 66:3, s. 720-731
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Tidskriftsartikel (refereegranskat)abstract
- Comparing patterns of diversity and divergence between populations at immune genes and neutral markers can give insights into the nature and geographic scale of parasite-mediated selection. To date, studies investigating such patterns of selection in vertebrates have primarily focused on the acquired branch of the immune system, whereas it remains largely unknown how parasite-mediated selection shapes innate immune genes both within and across vertebrate populations. Here, we present a study on the diversity and population differentiation at the innate immune gene Toll-like receptor 2 (TLR2) across nine populations of yellow-necked mice (Apodemus flavicollis) and bank voles (Myodes glareolus) in southern Sweden. In yellow-necked mice, TLR2 diversity was very low, as was TLR2 population differentiation compared to neutral loci. In contrast, several TLR2 haplotypes co-occurred at intermediate frequencies within and across bank vole populations, and pronounced isolation by distance between populations was observed. The diversity and differentiation at neutral loci was similar in the two species. These results indicate that parasite-mediated selection has been acting in dramatically different ways on a given immune gene in ecologically similar and sympatric species. Furthermore, the finding of TLR2 population differentiation at a small geographical scale in bank voles highlights that vertebrate innate immune defense may be evolutionarily more dynamic than has previously been appreciated.
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| 8. |
- Karlsson Espmark, Ann-Kristin, 1952, et al.
(författare)
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Hearing confirms existence and identity--experiences from persons with presbyacusis.
- 2003
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Ingår i: International journal of audiology. - 1499-2027. ; 42:2, s. 106-15
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present qualitative study was to describe how elderly persons with presbyacusis experience living with that type of hearing loss. The ultimate goal is for these experiences to be used in personal-adjustment counselling in audiological rehabilitation. The study included seven men and seven women with mild-to-moderate hearing impairment of the typical presbyacusis type. Open-ended interviews were conducted with each person. The interviewees were analysed according to the phenomenographic approach, and 10 categories emerged: 'Conversation takes away or maintains identity', 'It's other people's fault that I can't hear', 'Other people make you realize you can't hear', 'Society makes you think you shouldn't mind about your hearing loss', 'It's natural to hear badly when you are old', 'You should hear well all your life', 'You want to keep a feeling of continuity in your daily life in spite of your hearing loss', 'You don't need to hear everything', 'You want to hear so you feel that you're alive', and 'You want to hear so you understand and keep yourself informed'. All these categories deal with identity or existence and form the basis for how the hearing impairment is experienced and managed. The subjects protected their identity in various ways, but above all by blaming their poor hearing on old age, and managing it with simple everyday strategies that did not break the feeling of continuity in everyday life. Not until they experienced the lack of sound as a lack of contact with life was there any interest in help in the form of hearing technology. There is a need for information about the possibility of rehabilitating presbyacusis, as hearing is important not only for communication and spatial orientation, but also as affirmation of our existence as human beings.
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