Innate immunity and asthma risk in amish and hutterite farm children

Michelle M. Stein, Cara L. Hrusch, Justyna Gozdz, Catherine Igartua, Vadim Pivniouk, Sean E. Murray, Julie G. Ledford, Mauricius Marques Dos Santos, Rebecca L. Anderson, Nervana Metwali, Julia W. Neilson, Raina M. Maier, Jack A. Gilbert, Mark Holbreich, Peter S. Thorne, Fernando D. Martinez, Erika Von Mutius, Donata Vercelli, Carole Ober, Anne I. Sperling

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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 peripheralblood 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.

Original languageEnglish (US)
Pages (from-to)411-421
Number of pages11
JournalNew England Journal of Medicine
Volume375
Issue number5
DOIs
StatePublished - Aug 4 2016

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ASJC Scopus subject areas

  • Medicine(all)

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Stein, M. M., Hrusch, C. L., Gozdz, J., Igartua, C., Pivniouk, V., Murray, S. E., Ledford, J. G., Dos Santos, M. M., Anderson, R. L., Metwali, N., Neilson, J. W., Maier, R. M., Gilbert, J. A., Holbreich, M., Thorne, P. S., Martinez, F. D., Von Mutius, E., Vercelli, D., Ober, C., & Sperling, A. I. (2016). Innate immunity and asthma risk in amish and hutterite farm children. New England Journal of Medicine, 375(5), 411-421. https://doi.org/10.1056/NEJMoa1508749