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

Abstract

Background: Bacterial infections are supposed to act counterregulatory to the development of allergen-specific Th2 immune responses. We analyzed whether administration of extracellular Staphylococcus aureus inhibited experimental sensitization against allergens. Methods: BALB/c mice were immunized with alum-adsorbed ovalbumin (OVA) together with formalin-fixed Staphylococcus 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 Staphylococcus particles to modulate cytokine production by bone marrow-derived dendritic cells was analyzedin vitro. Results: Simultaneous application of OVA and Staphylococcus 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 Staphylococcus. An enhanced frequency or activity of regulatory T cells after administration of Staphylococcus particles was not apparent. Treatment of mice with Staphylococcus particles during the sensitization phase prevented lung inflammation (airway hyperreactivity, eosinophilia) after local challenge with OVA. Culture of bone marrow-derived dendritic cells with Staphylococcus particles induced IL-12p35 and p40 mRNA expression as well as secretion of IL-12p70, and increased production of IL-10 mRNA and protein. Conclusions: Administration of formalin-fixed Staphylococcus particles induced Th1-biased immune responses and prevented allergic sensitization.

Dendritic cells lentivirally engineered to overexpress interleukin‐10 inhibit contact hypersensitivity responses, despite their partial activation induced by transduction‐associated physical stress

“…Cells were grown in culture flasks (175 cm 3 ; Greiner, Nürtingen, Germany) and were split (1 : 100) every 5–7 days. BM‐DCs were generated from bone marrow progenitors of C57BL/6 mice as reported by Scheicher et al 18 with modifications as described elsewhere 19, except that DC culture supernatants were replenished on days 3 and 6, and part of the DC cultures was stimulated with LPS (1 µg/ml; Calbiochem, Schwalbach, Germany) on day 8 for 24 h to yield mature DCs (mDCs). The DC medium used was IMDM (Gibco/Invitrogen, Karlsruhe, Germany) supplemented with 10% FCS, 2 m M L ‐glutamine, 100 U/ml penicillin, 100 µg/ml streptomycin and 5% of GM‐CSF containing cell culture supernatant 20 (a kind gift by Dr B. Stockinger, MRC National Institute for Medical Research, London, UK).…”

Antigen dose‐dependent suppression of murine IgE responses is mediated by CD4−CD8− double‐negative T cells

“…After 72 h, cells were collected and total RNA was isolated using the NucleoSpin RNAII Total RNA Isolation Kit (Macherey‐Nagel, Düren, Germany) according to the protocol recommended by the manufacturer. RT‐PCR was performed as described before [16], using primer sequences published previously [12].…”

Staphylococcus aureus Colonization: Modulation of Host Immune Response and Impact on Human Vaccine Design

“…It may also predict a higher likelihood of atopic disease (188). Airway exposure to S. aureus enterotoxins has been linked to the development of asthma and allergic rhinitis, perhaps by inducing local Th1/Th17 responses (189–191). …”