Lipopolysaccharides Modulate Allergen-Specific Immune Regulation in a Murine Model of Mucosal Tolerance InductionGerhold K. · Avagyan A. · Reichert E. · Blümchen K. · Wahn U. · Hamelmann E.
Department of Pediatric Pneumology and Immunology, University Hospital Charité, Berlin, Germany
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-γ-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.
© 2008 S. Karger AG, Basel
Received: July 16, 2007
Accepted after revision: December 21, 2007
Published online: April 30, 2008
Number of Print Pages : 10
Number of Figures : 4, Number of Tables : 4, Number of References : 30
International Archives of Allergy and Immunology
Vol. 147, No. 1, Year 2008 (Cover Date: August 2008)
Journal Editor: Valenta R. (Vienna)
ISSN: 1018–2438 (Print), eISSN: 1423–0097 (Online)
For additional information: http://www.karger.com/IAA