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    Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children

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    Author
    Stein, Michelle M.
    Hrusch, Cara L.
    Gozdz, Justyna
    Igartua, Catherine
    Pivniouk, Vadim
    Murray, Sean E.
    Ledford, Julie G.
    Marques dos Santos, Mauricius
    Anderson, Rebecca L.
    Metwali, Nervana
    Neilson, Julia W.
    Maier, Raina M.
    Gilbert, Jack A.
    Holbreich, Mark
    Thorne, Peter S.
    Martinez, Fernando D.
    von Mutius, Erika
    Vercelli, Donata
    Ober, Carole
    Sperling, Anne I.
    Show allShow less
    Affiliation
    Univ Arizona, NIEHS Training Program Environm Toxicol
    Univ Arizona, Grad Program Cellular & Mol Med
    Univ Arizona, Dept Cellular & Mol Med
    Univ Arizona, Dept Med
    Univ Arizona, Dept Chem & Environm Engn
    Univ Arizona, Dept Soil Water & Environm Sci
    Issue Date
    2016-08-04
    
    Metadata
    Show full item record
    Publisher
    MASSACHUSETTS MEDICAL SOC
    Citation
    Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children 2016, 375 (5):411 New England Journal of Medicine
    Journal
    New England Journal of Medicine
    Rights
    Copyright © 2016 Massachusetts Medical Society.
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.
    Note
    August 4, 2016. 6 Month Embargo.
    ISSN
    0028-4793
    1533-4406
    PubMed ID
    27518660
    DOI
    10.1056/NEJMoa1508749
    Version
    Final published version
    Sponsors
    National Institutes of Health
    Additional Links
    http://www.nejm.org/doi/10.1056/NEJMoa1508749
    ae974a485f413a2113503eed53cd6c53
    10.1056/NEJMoa1508749
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