Journal article
Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children
The New England journal of medicine, Vol.375(5), pp.411-421
08/04/2016
DOI: 10.1056/NEJMoa1508749
PMCID: PMC5137793
PMID: 27518660
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.
Details
- Title: Subtitle
- Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children
- Creators
- Michelle M Stein - Univ Chicago, Dept Human Genet, 920 E 58th St,CLSC 425, Chicago, IL 60637 USACara L Hrusch - Univ Chicago, Dept Med, Sect Pulm & Crit Care Med, Chicago, IL 60637 USAJustyna Gozdz - Univ Arizona, NIEHS Training Program Environm Toxicol, Tucson, AZ 85721 USACatherine Igartua - Univ Chicago, Dept Human Genet, 920 E 58th St,CLSC 425, Chicago, IL 60637 USAVadim Pivniouk - Univ Arizona, Dept Cellular & Mol Med, Tucson, AZ 85721 USASean E Murray - Arizona Resp Ctr, Tucson, AZ USAJulie G Ledford - Univ Arizona, Dept Med, Tucson, AZ 85721 USAMauricius Marques dos Santos - University of ArizonaRebecca L Anderson - Univ Chicago, Dept Human Genet, 920 E 58th St,CLSC 425, Chicago, IL 60637 USANervana Metwali - University of Iowa, Occupational and Environmental HealthJulia W Neilson - Univ Arizona, Dept Soil Water & Environm Sci, Tucson, AZ 85721 USARaina M Maier - Univ Arizona, Dept Soil Water & Environm Sci, Tucson, AZ 85721 USAJack A Gilbert - Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USAMark Holbreich - Allergy & Asthma Consultants, Indianapolis, IN USAPeter S Thorne - University of Iowa, Occupational and Environmental HealthFernando D Martinez - Arizona Resp Ctr, Tucson, AZ USAErika von Mutius - Univ Munich, Dr von Hauner Childrens Hosp, Munich, GermanyDonata Vercelli - Univ Arizona, Dept Cellular & Mol Med, Tucson, AZ 85721 USACarole Ober - Univ Chicago, Dept Human Genet, 920 E 58th St,CLSC 425, Chicago, IL 60637 USAAnne I Sperling - Univ Chicago, Dept Med, Sect Pulm & Crit Care Med, Chicago, IL 60637 USA
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.375(5), pp.411-421
- Publisher
- MASSACHUSETTS MEDICAL SOC
- DOI
- 10.1056/NEJMoa1508749
- PMID
- 27518660
- PMCID
- PMC5137793
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Number of pages
- 11
- Grant note
- National Institutes of Health
- Language
- English
- Date published
- 08/04/2016
- Academic Unit
- Civil and Environmental Engineering; Occupational and Environmental Health
- Record Identifier
- 9983997327402771
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