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  • Title: Lipopolysaccharides modulate allergen-specific immune regulation in a murine model of mucosal tolerance induction.
    Author: Gerhold K, Avagyan A, Reichert E, Blumchen K, Wahn U, Hamelmann E.
    Journal: Int Arch Allergy Immunol; 2008; 147(1):25-34. PubMed ID: 18446050.
    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. CONCLUSION: 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.
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