Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children
AuthorStein, Michelle M.
Hrusch, Cara L.
Murray, Sean E.
Ledford, Julie G.
Marques dos Santos, Mauricius
Anderson, Rebecca L.
Neilson, Julia W.
Maier, Raina M.
Gilbert, Jack A.
Thorne, Peter S.
Martinez, Fernando D.
von Mutius, Erika
Sperling, Anne I.
AffiliationUniv 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
MetadataShow full item record
PublisherMASSACHUSETTS MEDICAL SOC
CitationInnate Immunity and Asthma Risk in Amish and Hutterite Farm Children 2016, 375 (5):411 New England Journal of Medicine
JournalNew England Journal of Medicine
RightsCopyright © 2016 Massachusetts Medical Society.
Collection InformationThis 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 firstname.lastname@example.org.
AbstractBACKGROUND 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.
NoteAugust 4, 2016. 6 Month Embargo.
VersionFinal published version
SponsorsNational Institutes of Health
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