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RESEARCH PRODUCT

Formalin-Fixed <i>Staphylococcus aureus</i> Particles Prevent Allergic Sensitization in a Murine Model of Type I Allergy

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<i>Background:</i> Bacterial infections are supposed to act counterregulatory to the development of allergen-specific Th2 immune responses. We analyzed whether administration of extracellular <i>Staphylococcus aureus</i> inhibited experimental sensitization against allergens. <i>Methods:</i> BALB/c mice were immunized with alum-adsorbed ovalbumin (OVA) together with formalin-fixed <i>Staphylococcus</i> particles. OVA-specific antibody production and cytokine synthesis by spleen cells was analyzed. Airway reactivity and cellular infiltration into the airways was assessed after intranasal challenge of mice with OVA. In addition, the capacity of <i>Staphylococcus</i> particles to modulate cytokine production by bone marrow-derived dendritic cells was analyzedin vitro. <i>Results:</i> Simultaneous application of OVA and <i>Staphylococcus</i> particles very efficiently inhibited production of specific IgE and IgG1 as well as secretion of IL-4 and IL-5 by splenocytes, while enhancing IgG2a formation and production of IFN-γ, indicating a shift from a Th2 response towards a Th1-biased response. This effect was not dependent on the expression of protein A by <i>Staphylococcus</i>. An enhanced frequency or activity of regulatory T cells after administration of <i>Staphylococcus</i> particles was not apparent. Treatment of mice with <i>Staphylococcus</i> particles during the sensitization phase prevented lung inflammation (airway hyperreactivity, eosinophilia) after local challenge with OVA. Culture of bone marrow-derived dendritic cells with <i>Staphylococcus</i> particles induced IL-12p35 and p40 mRNA expression as well as secretion of IL-12p70, and increased production of IL-10 mRNA and protein. <i>Conclusions:</i> Administration of formalin-fixed <i>Staphylococcus</i> particles induced Th1-biased immune responses and prevented allergic sensitization.