Expression of genes related to anti-inflammatory pathways are modified among farmers' children

PLoS One. 2014 Mar 6;9(3):e91097. doi: 10.1371/journal.pone.0091097. eCollection 2014.

Abstract

Background: The hygiene hypothesis states that children exposed to higher loads of microbes such as farmers' children suffer less from allergies later in life. Several immunological mechanisms underpinning the hygiene hypothesis have been proposed such as a shift in T helper cell balance, T regulatory cell activity, or immune regulatory mechanisms induced by the innate immunity.

Objective: To investigate whether the proposed immunological mechanisms for the hygiene hypotheses are found in farmers' children.

Methods: We assessed gene expression levels of 64 essential markers of the innate and adaptive immunity by quantitative real-time PCR in white blood cells in 316 Swiss children of the PARSIFAL study to compare farmers' to non-farmers' expressions and to associate them to the prevalence of asthma and rhinoconjunctivitis, total and allergen-specific IgE in serum, and expression of Cε germ-line transcripts.

Results: We found enhanced expression of genes of the innate immunity such as IRAK-4 and RIPK1 and enhanced expression of regulatory molecules such as IL-10, TGF-β, SOCS4, and IRAK-2 in farmers' children. Furthermore, farmers' children expressed less of the TH1 associated cytokine IFN-γ while TH2 associated transcription factor GATA3 was enhanced. No significant associations between the assessed immunological markers and allergic diseases or sensitization to allergens were observed.

Conclusion: Farmers' children express multiple increased innate immune response and immune regulatory molecules, which may contribute to the mechanisms of action of the hygiene hypothesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agriculture*
  • Allergens / immunology
  • Asthma / genetics
  • Child
  • Child, Preschool
  • Conjunctivitis / genetics
  • Cytokines / metabolism
  • Female
  • Gene Expression Regulation*
  • Humans
  • Immunoglobulin Class Switching / genetics
  • Immunoglobulin E / genetics
  • Immunoglobulin E / metabolism
  • Inflammation / genetics*
  • Male
  • Receptors, Pattern Recognition / genetics
  • Receptors, Pattern Recognition / metabolism
  • Signal Transduction / genetics*
  • Th1 Cells / immunology
  • Th2 Cells / immunology
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism
  • Workforce

Substances

  • Allergens
  • Cytokines
  • Receptors, Pattern Recognition
  • Toll-Like Receptors
  • Immunoglobulin E

Grants and funding

Supported by grants from the European Union QLRT 1999–013, from the Swiss National Science Foundation 2-100324, and by the Christine Kühne – Center for Allergy Research and Education (CK-Care) in Davos. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.