title: Lipopolysaccharides modulate allergen-specific immune regulation in a murine model of mucosal tolerance induction.
abstract: BACKGROUND
  Farming has been widely reported to be associated with decreased risk of developing atopic disorders, but underlying immunomodulatory mechanisms are still not fully defined. We delineated T-cell functions after induction of mucosal tolerance in the context of intranasally delivered organic dust compounds, lipopolysaccharides (LPS).
  
  
  METHODS
  BALB/c mice were pretreated intranasally with ovalbumin (OVA) with or without LPS (Escherichia coli) three times (days -21, -14, -7) prior to systemic OVA sensitization (days 1 and 14) and airway allergen challenges (days 28-30). CD4+ spleen T cells from pretreated and sensitized donors were characterized for cytokine function, and transferred into naive recipients prior to subsequent OVA sensitization and challenges.
  
  
  RESULTS
  Intranasal OVA pretreatment suppressed Th2-mediated immune and inflammatory responses and enhanced frequency of regulatory T cells in OVA-sensitized and -challenged mice. Addition of LPS to OVA, but not LPS alone, inhibited development of allergen-induced sensitization and eosinophilic airway infiltration, and markedly enhanced allergen-specific IgG1 serum levels and frequencies of IL-10- and IFN-gamma-producing CD4+ T cells. Transfer of CD4+ spleen T cells from OVA-pretreated animals protected naive recipients against subsequent allergen sensitization and airway disease, whereas transfer from LPS/OVA-pretreated animals only protected against allergen sensitization.
  
  
  CONCLUSIONS
  Microbial LPS modulated mucosal tolerance by inducing allergen-specific IgG1 production and distinct effector CD4+ T cells with a mixed regulatory/Th1 phenotype. Organic dust components such as LPS might therefore be important immune modulators in naturally occurring or preventive allergen-specific tolerance induction.
authors.affiliation: Department of Pediatric Pneumology and Immunology, University Hospital Charité, Berlin, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Gerhold
authors.forename: Angela
authors.initials: A
authors.lastname: Avagyan
authors.forename: Eva
authors.initials: E
authors.lastname: Reichert
authors.forename: Katharina
authors.initials: K
authors.lastname: Blumchen
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wahn
authors.forename: Eckard
authors.initials: E
authors.lastname: Hamelmann
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology
chemical_list: D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D010047:Ovalbumin