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dc.contributor.authorStein, Michelle M.
dc.contributor.authorHrusch, Cara L.
dc.contributor.authorGozdz, Justyna
dc.contributor.authorIgartua, Catherine
dc.contributor.authorPivniouk, Vadim
dc.contributor.authorMurray, Sean E.
dc.contributor.authorLedford, Julie G.
dc.contributor.authorMarques dos Santos, Mauricius
dc.contributor.authorAnderson, Rebecca L.
dc.contributor.authorMetwali, Nervana
dc.contributor.authorNeilson, Julia W.
dc.contributor.authorMaier, Raina M.
dc.contributor.authorGilbert, Jack A.
dc.contributor.authorHolbreich, Mark
dc.contributor.authorThorne, Peter S.
dc.contributor.authorMartinez, Fernando D.
dc.contributor.authorvon Mutius, Erika
dc.contributor.authorVercelli, Donata
dc.contributor.authorOber, Carole
dc.contributor.authorSperling, Anne I.
dc.date.accessioned2016-12-02T00:29:12Z
dc.date.available2016-12-02T00:29:12Z
dc.date.issued2016-08-04
dc.identifier.citationInnate Immunity and Asthma Risk in Amish and Hutterite Farm Children 2016, 375 (5):411 New England Journal of Medicineen
dc.identifier.issn0028-4793
dc.identifier.issn1533-4406
dc.identifier.pmid27518660
dc.identifier.doi10.1056/NEJMoa1508749
dc.identifier.urihttp://hdl.handle.net/10150/621477
dc.description.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.
dc.description.sponsorshipNational Institutes of Healthen
dc.language.isoenen
dc.publisherMASSACHUSETTS MEDICAL SOCen
dc.relation.urlhttp://www.nejm.org/doi/10.1056/NEJMoa1508749en
dc.rightsCopyright © 2016 Massachusetts Medical Society.en
dc.titleInnate Immunity and Asthma Risk in Amish and Hutterite Farm Childrenen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, NIEHS Training Program Environm Toxicolen
dc.contributor.departmentUniv Arizona, Grad Program Cellular & Mol Meden
dc.contributor.departmentUniv Arizona, Dept Cellular & Mol Meden
dc.contributor.departmentUniv Arizona, Dept Meden
dc.contributor.departmentUniv Arizona, Dept Chem & Environm Engnen
dc.contributor.departmentUniv Arizona, Dept Soil Water & Environm Scien
dc.identifier.journalNew England Journal of Medicineen
dc.description.noteAugust 4, 2016. 6 Month Embargo.en
dc.description.collectioninformationThis 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.en
dc.eprint.versionFinal published versionen
refterms.dateFOA2017-02-05T00:00:00Z
html.description.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.


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