Genetic Diversity in Cytokines Associated with Immune Variation and Resistance to Multiple Pathogens in a Natural Rodent Population

Turner, Alan; Begon, Michael; Jackson, Joe; Bradley, Janette E.; Paterson, Steve

doi:10.1371/journal.pgen.1002343

Cited by 90 publications

(117 citation statements)

References 79 publications

(96 reference statements)

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“…On the other hand, we analyzed FAS-L expression at the basal state, without stimulation in peripheral blood leukocytes. Besides differences in the protocols used for the analysis of gene expression, a combination of SNPs may affect the production of the molecule, 25 environmental agents can modify gene expression, 26 and different intracellular mechanisms may interfere with maintenance or degradation of mRNAs and proteins. 27 Indeed, several factors influence the production of a particular protein, and this influence can hinder the detection of a genotype/phenotype correlation.…”

Section: Discussionmentioning

confidence: 99%

FAS and FAS-L Genotype and Expression in Patients With Recurrent Pregnancy Loss

et al. 2013

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We assessed FAS and FAS-L gene polymorphisms and messenger RNA (mRNA) levels in patients with recurrent pregnancy loss (RPL). This case-control study compared 129 women with RPL with 235 healthy multiparous women (control group). Genomic DNA and total mRNA were extracted from whole blood, and polymorphisms genotyping was performed by polymerase chain reaction (PCR). Messenger RNA expression levels were analyzed by real-time PCR. Data were analyzed by chi-square and Fisher exact tests; P < .05 was considered significant. There were no significant differences in the FAS (670 A/G) genotype or allelic frequencies between the RPL and control groups. We found significant differences in the FAS-L (844 C/T) genotype and allelic frequencies between women with RPL and controls. Patients with RPL had significantly higher FAS-L expression. Our data suggest that FAS-L gene polymorphism is associated with increased susceptibility to RPL. Moreover, women with RPL seem to abnormally express FAS-FAS-L molecules.

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Section: Discussionmentioning

confidence: 99%

FAS and FAS-L Genotype and Expression in Patients With Recurrent Pregnancy Loss

et al. 2013

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“…Similarly, in the present study, we detected a significant association between allele AA*05 and infection with Babesia ssp. Recently, Turner et al (2011) showed that the susceptibility to Babesia microti in common vole was associated with the variation within genes coding interleukines Il2 and Il2b.…”

Section: Effects Of the Mhc On Infection And Survival Ratesmentioning

confidence: 99%

MHC influences infection with parasites and winter survival in the root vole Microtus oeconomus

et al. 2012

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Selective pressure from parasites is thought to maintain the polymorphism of major histocompatibility complex (MHC) genes. Although a number of studies have shown a relationship between the MHC and parasitic infections, the fitness consequences of such associations are less well documented. In the present paper, we characterised the variation in exon 2 of MHC class II DRB gene in the root vole and examined the effects of that gene on parasite prevalence and winter survival. We identified 18 unique exon 2 sequences, which translated into 10 unique amino acid sequences. Phylogenetic analysis revealed the presence of three distinct clusters, and allele distributions among these individuals suggested that the clusters correspond to three different loci. Although the rate of synonymous substitutions (d S ) exceeded the rate of nonsynonymous substitutions (d N ) across sequences, implying purifying selection, d N was significantly elevated at antigen-binding sites, suggesting that these sites could be under positive selection. Screening for parasites revealed a moderate prevalence of infection with gastrointestinal parasites (24 % infected), but a high infection rate for blood parasites (56 % infected). Infection with the blood parasite Babesia ssp. decreased survival almost twofold (25.7 vs. 13.9 %). Animals possessing the amino acid sequence AA*08 survived better than others (44.9 vs. 22 %), and they were infected with Babesia ssp. less often (13.9 vs 25.7 %). In contrast, individuals carrying allele AA*05 were infected more often (31.7 vs. 15.3 %). Heterozygosity at one of the putative loci was associated with a lower probability of infection with Babesia ssp., but at the other locus, the association was reversed. The unexpected latter result could be at least partly explained by the increased frequency of the susceptible allele AA*05 among heterozygotes. Overall, we demonstrate that infection with Babesia ssp. is a strong predictor of Electronic supplementary material The online version of this article

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“…To elucidate the evolutionary causes and consequences of such variation, a better understanding of which genes actually contribute to variation in resistance is desirable [2][3][4]. However, whereas there is a considerable body of literature on the genetic basis of resistance in humans [5], knowledge from other animals, and in particular from natural vertebrate populations, is as yet very limited (but see [6]). …”

Section: Introductionmentioning

confidence: 99%

Polymorphisms at the innate immune receptorTLR2are associated withBorreliainfection in a wild rodent population

et al. 2013

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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-markrecapture 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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Genetic Diversity in Cytokines Associated with Immune Variation and Resistance to Multiple Pathogens in a Natural Rodent Population

Cited by 90 publications

References 79 publications

FAS and FAS-L Genotype and Expression in Patients With Recurrent Pregnancy Loss

FAS and FAS-L Genotype and Expression in Patients With Recurrent Pregnancy Loss

MHC influences infection with parasites and winter survival in the root vole Microtus oeconomus

Polymorphisms at the innate immune receptorTLR2are associated withBorreliainfection in a wild rodent population

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