Dysregulation of allergic airway inflammation in the absence of microbial colonization

Tina Herbst, Anke Sichelstiel, Corinne Schär, Koshika Yadava, Kurt Bürki, Julia Cahenzli, Kathy McCoy, Benjamin J. Marsland, Nicola L. Harris

Research output: Contribution to journalArticleResearchpeer-review

255 Citations (Scopus)

Abstract

Rationale: The incidence of allergic disorders is increasing in developed countries and has been associated with reduced exposure to microbes and alterations in the commensal bacterial flora. Objectives: To ascertain the relevance of commensal bacteria on the development of an allergic response, we used a model of allergic airway inflammation in germ-free (GF) mice that lack any exposure to pathogenic or nonpathogenic microorganisms. Methods: Allergic airway inflammation was induced in GF, specific pathogen-free (SPF), or recolonized mice by sensitization and challenge with ovalbumin. The resulting cellular infiltrate and cytokine production were measured. Measurements and Main Results: Our results show that the total number of infiltrating lymphocytes and eosinophils were elevated in the airways of allergic GF mice compared with control SPF mice, and that this increase could be reversed by recolonization of GF mice with the complex commensal flora of SPF mice. Exaggerated airway eosinophilia correlated with increased local production of Th2-associated cytokines, elevated IgE production, and an altered number and phenotype of conventional dendritic cells. Regulatory T-cell populations and regulatory cytokine levels were unaltered, but GF mice exhibited an increased number of basophils and decreased numbers of alveolar macrophages and plasmacytoid dendritic cells. Conclusions: These data demonstrate that the presence of commensal bacteria is critical for ensuring normal cellular maturation, recruitment, and control of allergic airway inflammation.

Original languageEnglish
Pages (from-to)198-205
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume184
Issue number2
DOIs
Publication statusPublished - 15 Jul 2011
Externally publishedYes

Keywords

  • Allergic airway inflammation
  • Alveolar macrophages
  • Commensal dysbiosis
  • Dendritic cells

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