Dysregulation of Allergic Airway Inflammation in the Absence of Microbial Colonization

• Published in: American journal of respiratory and critical care medicine 2011-07, Vol.184 (2), p.198-205
• Main Authors: HERBST, Tina, SICHELSTIEL, Anke, SCHÄR, Corinne, YADAVA, Koshika, BÜRKI, Kurt, CAHENZLI, Julia, MCCOY, Kathy, MARSLAND, Benjamin J, HARRIS, Nicola L
• Format: Article
• Language: English
• Subjects: Aluminum; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Asthma - complications; Asthma - immunology; Bacteria; Basophils - immunology; Biological and medical sciences; Cytokines; Dendritic cells; Dendritic Cells - immunology; Disease Models, Animal; Emergency and intensive respiratory care; Enzyme-Linked Immunosorbent Assay; Eosinophils - immunology; Flow Cytometry; Immunization; Immunoglobulin E - immunology; Inflammation; Inflammation - complications; Inflammation - immunology; Intensive care medicine; Laboratory animals; Lung - immunology; Macrophages, Alveolar - immunology; Medical sciences; Metagenome - immunology; Mice; Mice, Inbred C57BL; Microbiota; Microorganisms; Ovalbumin; Pathogens; Specific Pathogen-Free Organisms; T-Lymphocytes, Regulatory - immunology; Th2 Cells - immunology
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.201010-1574oc

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. 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. 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. 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. These data demonstrate that the presence of commensal bacteria is critical for ensuring normal cellular maturation, recruitment, and control of allergic airway inflammation.