Objectives: Allergic asthma is a frequent and heterogeneous chronic inflammatory airway disease. Drivers of inflammation and their immunological modes of action are of special interest. Significant relationships between the gram-positive opportunistic pathogen Staphylococcus aureus and asthma have been recognized. However, the mechanisms underlying associations between S. aureus nasal carriage, S. aureus toxin-exposure, toxin-specific sensitization and inflammation in allergic asthma remain elusive.
Methods: We recruited 62 patients with allergic asthma and 36 non-asthma controls, in whom we assessed S. aureus nasal colonization, local and systemic inflammatory parameters, sensitization to aeroallergens and S. aureus toxins. We colonized C57BL/6 mice with a murine S. aureus isolate or treated them intranasally with S. aureus enterotoxin B (SEB) and assessed effects on ovalbumin-mediated allergic airway inflammation.
Results: In patients as well as the mouse model, S. aureus carriage had limited effects on allergic airway inflammation. In patients, toxin-specific sensitization was associated with increased peripheral eosinophil numbers. In mice, administration of the toxin SEB significantly boosted the OVA-specific IgE response and led to a significantly reduced recruitment of immune cells and a significantly dampened Th-2 cytokine response in allergic airway inflammation. These effects were likely due to lasting modulation of the local respiratory immune milieu, as administration of SEB alone resulted in a significantly altered respiratory cellular composition and cytokine milieu up to 14 days after treatment.
Conclusions: In mice, SEB holds a previously unrecognized potential to sustainably modulate the respiratory immune milieu significantly affecting allergic airway inflammation. In clinical samples, S. aureus toxin-specific sensitization seems to exert stronger effects on inflammation than S. aureus colonization.