Genetic diversity in cytokines associated with immune variation and resistance to multiple pathogens in a natural rodent population.
Genetic diversity in cytokines associated with immune variation and resistance to multiple pathogens in a natural rodent population.
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DOI：
10.1371/journal.pgen.1002343
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发表时间：
2011-10
期刊：
影响因子：
4.5
通讯作者：
Paterson S
中科院分区：
文献类型：
--
作者：
Turner AK;Begon M;Jackson JA;Bradley JE;Paterson S
病原体被认为驱动了宿主基因座的遗传多样性，这些基因座涉及对传染病的免疫。迄今为止，探索病原体抗性遗传基础的研究几乎完全集中在主要组织相容性复合体（MHC）的基因上;基因组中其他地方的遗传变异作为病原体抗性变异基础的作用很少在自然种群中进行探索。细胞因子是在许多免疫和生理过程中发挥作用的信号分子。在这里，我们使用一个自然种群的田鼠（Microtus agrestis），研究如何在一套细胞因子和其他免疫位点的遗传多样性影响免疫反应表型和抵抗几个地方病病原体物种。通过使用线性模型首先控制一系列非遗传因素，我们证明了细胞因子位点的遗传变异对宿主免疫参数和对多种病原体的抗性的强烈影响。这些影响主要局限于三个细胞因子基因（白细胞介素1 β（IL 1b），IL 2和IL 12 b），而不是其他细胞因子测试，或膜结合，非细胞因子免疫位点。观察到的遗传效应与性别和体重等其他内在因素一样大。我们的研究结果表明，在细胞因子基因座的遗传多样性是一个新的和重要的来源，在自然人群中的免疫功能和病原体抗性的个体差异。因此，这些基因座的产物可能会影响病原体之间的相互作用，并有助于确定自然种群的生存和繁殖成功。我们的研究还强调了野生啮齿动物作为生态免疫学模型的实用性，以更好地了解包括人类在内的自然群体免疫功能变异的原因和后果。我们对感染免疫的遗传基础的了解，大部分来自对实验室动物的研究。然而，这些动物的饲养条件与自然环境中的条件非常不同。为了提高我们对疾病易感性的遗传决定因素的理解，因此重要的是要研究遗传变异如何影响自然人群的免疫力。到目前为止，对野外病原体抗性遗传基础的研究几乎完全集中在主要组织相容性复合体（MHC）的基因上。MHC在感染免疫中无疑是重要的，但还有许多其他参与免疫反应的基因尚待研究。在这里，我们研究了细胞因子的遗传变异，细胞因子是诱导和调节免疫反应不同效应臂的关键信号分子。我们使用一个自然种群的田鼠，野生啮齿动物相关的常见实验室物种，并表明细胞因子基因内的变异与个体之间的差异，在他们的免疫反应和抵抗多种病原体。细胞因子可能是遗传变异的重要来源，以帮助个体对抗感染并在野外生存。
Pathogens are believed to drive genetic diversity at host loci involved in immunity to infectious disease. To date, studies exploring the genetic basis of pathogen resistance in the wild have focussed almost exclusively on genes of the Major Histocompatibility Complex (MHC); the role of genetic variation elsewhere in the genome as a basis for variation in pathogen resistance has rarely been explored in natural populations. Cytokines are signalling molecules with a role in many immunological and physiological processes. Here we use a natural population of field voles (Microtus agrestis) to examine how genetic diversity at a suite of cytokine and other immune loci impacts the immune response phenotype and resistance to several endemic pathogen species. By using linear models to first control for a range of non-genetic factors, we demonstrate strong effects of genetic variation at cytokine loci both on host immunological parameters and on resistance to multiple pathogens. These effects were primarily localized to three cytokine genes (Interleukin 1 beta (Il1b), Il2, and Il12b), rather than to other cytokines tested, or to membrane-bound, non-cytokine immune loci. The observed genetic effects were as great as for other intrinsic factors such as sex and body weight. Our results demonstrate that genetic diversity at cytokine loci is a novel and important source of individual variation in immune function and pathogen resistance in natural populations. The products of these loci are therefore likely to affect interactions between pathogens and help determine survival and reproductive success in natural populations. Our study also highlights the utility of wild rodents as a model of ecological immunology, to better understand the causes and consequences of variation in immune function in natural populations including humans. Much of what we know about the genetic basis of immunity to infection has come from studies of laboratory animals. However, these animals are kept in conditions very different from those experienced in the natural environment. In order to improve our understanding of the genetic determinants of disease susceptibility, it is therefore important to examine how genetic variation impacts on immunity in natural populations. So far, studies into the genetic basis of pathogen resistance in the wild have focussed almost exclusively on genes of the Major Histocompatibility Complex (MHC). The MHC is undoubtedly important in immunity to infection, but there are many other genes involved in the immune response that are yet to be investigated. Here we examine genetic variation in cytokines, signalling molecules crucial in the induction and regulation of the different effector arms of the immune response. We use a natural population of field voles, wild rodents related to common laboratory species, and show that variation within cytokine genes is linked to differences between individuals in their immune response and in resistance to multiple pathogens. Cytokines are then likely to be an important source of genetic variation to help individuals combat infection and survive in the wild.
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影响因子：
5.4
作者：
BLACK, WC;KRAFSUR, ES
通讯作者：
KRAFSUR, ES
影响因子：
2.5
作者：
Corwin, E J
通讯作者：
Corwin, E J
影响因子：
4.4
作者：
Bown, K. J.;Lambin, X.;Birtles, R. J.
通讯作者：
Birtles, R. J.
DOI：
10.1111/j.2517-6161.1964.tb00553.x
发表时间：
1964-01-01
影响因子：
5.8
作者：
BOX, GEP;COX, DR
通讯作者：
COX, DR
影响因子：
2.4
作者：
Coltman, DW;Wilson, K;Pemberton, JM
通讯作者：
Pemberton, JM