Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children

被引:365
作者
Ege, MJ
Bieli, C
Frei, R
van Strien, RT
Riedler, J
Üblagger, E
Schram-Bijkerk, D
Brunekreef, B
van Hage, M
Scheynius, A
Pershagen, G
Benz, MR
Lauener, R
von Mutius, E
Braun-Fahrländer, C
机构
[1] Univ Childrens Hosp Munich, Munich, Germany
[2] Univ Basel, Inst Social & Prevent Med, CH-4003 Basel, Switzerland
[3] Univ Zurich, Childrens Hosp, CH-8006 Zurich, Switzerland
[4] Childrens Hosp, Schwarzach, Austria
[5] Childrens Hosp, Salzburg, Austria
[6] Univ Utrecht, Inst Risk Assessment Sci, NL-3508 TC Utrecht, Netherlands
[7] Karolinska Inst, Dept Med, Clin Allergy Res Unit, Stockholm, Sweden
[8] Univ Hosp, Stockholm, Sweden
[9] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden
关键词
asthma; allergy; atopic sensitization; gene expression; Toll-like receptors; CD14; farming; maternal exposure; microbial exposure;
D O I
10.1016/j.jaci.2005.12.1307
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: There is increasing evidence that environmental exposures determining childhood illnesses operate early in life. Prenatal exposure to a farming environment through the mother might also play an important role. Objective: We sought to investigate the role of maternal exposures to environments rich in microbial compounds for the development of atopic sensitization, asthma, and corresponding alterations in the innate immune system in offspring. Methods: In the children of the cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Life Style study, asthma and atopy were assessed by means of standardized questionnaires (n = 8263) and serum IgE measurements (n = 2086). In a subsample (n = 322) gene expression of Toil-like receptors (TLR2 and TLR4) and CD14 was assessed. Maternal exposures were defined through questionnaire information. Results: Both atopic sensitization (adjusted odds ratio, 0.58; 95% CI, 0.39-0.86) and the gene expression of receptors of innate immunity were strongly determined by maternal exposure to stables during pregnancy, whereas current exposures had much weaker or no effects. A dose-response relation was found between the extent of upregulation of these genes and the number of different farm animal species the mother had encountered in her pregnancy. Each additional farm animal species increased the expression of TLR2, TLR4, and CD14 by a factor of 1.16 (95% CI, 1.07-1.26), 1.12 (95% Cl, 1.04-1.2), and 1.10 (95% Cl, 1.03-1.23), respectively. Conclusion: Maternal exposure to an environment rich in microbial compounds might protect against the development of atopic sensitization and lead to upregulation of receptors of the innate immune system. The underlying mechanisms potentially operating through the intrauterine milieu or epigenetic inheritance await further elucidation. Clinical implications: When assessing risk factors of allergies in an infant's medical history, attention must also be paid to environmental exposures affecting the mother.
引用
收藏
页码:817 / 823
页数:7
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