Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children.
Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children.
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DOI：
10.1056/nejmoa1508749
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发表时间：
2016-08-04
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影响因子：
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通讯作者：
Sperling AI
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作者：
Stein MM;Hrusch CL;Gozdz J;Igartua C;Pivniouk V;Murray SE;Ledford JG;Marques Dos Santos M;Anderson RL;Metwali N;Neilson JW;Maier RM;Gilbert JA;Holbreich M;Thorne PS;Martinez FD;von Mutius E;Vercelli D;Ober C;Sperling AI
阿米什人和哈特人是美国的农业人口，他们的生活方式在许多方面非常相似，但他们的农业实践尤其不同;前者遵循传统的农业实践，而后者使用工业化的农业实践。这些人群在哮喘的患病率方面也显示出惊人的差异，而对这些差异背后的免疫反应知之甚少。我们研究了60名阿米什人和赫特人儿童的环境暴露、遗传血统和免疫特征，测量了过敏原和内毒素水平，并评估了室内灰尘样本的微生物组组成。收集全血以测量血清IgE水平、细胞因子应答和基因表达，并用流式细胞术对外周血白细胞进行表型分析。在实验性过敏性哮喘的小鼠模型中，评估了从阿米什人和哈特人家中获得的灰尘提取物对免疫和气道反应的影响。尽管阿米什人和哈特派儿童的遗传祖先和生活方式相似，但阿米什人哮喘和过敏性致敏的患病率分别为阿米什人的4倍和6倍，而阿米什人房屋灰尘中的内毒素水平中位数为6.8倍。在阿米什人和哈特人家中的灰尘样本中也观察到微生物组成的差异。在两组儿童之间还发现了先天免疫细胞的比例、表型和功能的深刻差异。在实验性过敏性哮喘的小鼠模型中，鼻内滴注来自阿米什人而非哈特人家庭的粉尘提取物可显著抑制气道高反应性和嗜酸性粒细胞增多。这些保护作用在MyD 88和Trif缺陷的小鼠中被废除，MyD 88和Trif是先天免疫信号传导的关键分子。我们对人类和小鼠的研究结果表明，阿米什人的环境通过参与和塑造先天免疫反应来提供对哮喘的保护。（由美国国立卫生研究院和其他机构资助。
The Amish and Hutterites are U.S. agricultural populations whose lifestyles are remarkably similar in many respects but whose farming practices, in particular, are distinct; the former follow traditional farming practices whereas the latter use industrialized farming practices. The populations also show striking disparities in the prevalence of asthma, and little is known about the immune responses underlying these disparities. We studied environmental exposures, genetic ancestry, and immune profiles among 60 Amish and Hutterite children, measuring levels of allergens and endotoxins and assessing the microbiome composition of indoor dust samples. Whole blood was collected to measure serum IgE levels, cytokine responses, and gene expression, and peripheral-blood leukocytes were phenotyped with flow cytometry. The effects of dust extracts obtained from Amish and Hutterite homes on immune and airway responses were assessed in a murine model of experimental allergic asthma. Despite the similar genetic ancestries and lifestyles of Amish and Hutterite children, the prevalence of asthma and allergic sensitization was 4 and 6 times as low in the Amish, whereas median endotoxin levels in Amish house dust was 6.8 times as high. Differences in microbial composition were also observed in dust samples from Amish and Hutterite homes. Profound differences in the proportions, phenotypes, and functions of innate immune cells were also found between the two groups of children. In a mouse model of experimental allergic asthma, the intranasal instillation of dust extracts from Amish but not Hutterite homes significantly inhibited airway hyperreactivity and eosinophilia. These protective effects were abrogated in mice that were deficient in MyD88 and Trif, molecules that are critical in innate immune signaling. The results of our studies in humans and mice indicate that the Amish environment provides protection against asthma by engaging and shaping the innate immune response. (Funded by the National Institutes of Health and others.)