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Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children
Michelle M Stein1, Cara L Hrusch1, Justyna Gozdz1
1Department of Human Genetics (M.M. Stein, C.I., R.L.A., C.O.), the Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology (C.L.H., A.I.S.), the Department of Ecology and Evolution (J.A.G.), and the Department of Surgery (J.A.G.), University of Chicago, Chicago, and the Institute for Genomic and Systems Biology, Argonne National Laboratory, Argonne (J.A.G.) - all in Illinois; the NIEHS Training Program in Environmental Toxicology and Graduate Program in Cellular and Molecular Medicine (J.G.), and the Departments of Cellular and Molecular Medicine (V.P., D.V.), Medicine (J.G.L.), Chemical and Environmental Engineering (M. Marques dos Santos), and Soil, Water, and Environmental Science (J.W.N., R.M.M.), University of Arizona, and the Arizona Respiratory Center and Bio5 Institute (J.G., V.P., S.E.M., J.G.L., F.D.M., D.V.) - all in Tucson; the Department of Occupational and Environmental Health, University of Iowa, Iowa City (N.M., P.S.T.); Allergy and Asthma Consultants, Indianapolis (M.H.); and Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany (E.M.).
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. (Funded by the National Institutes of Health and others.).
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