Modulation of allergic airway inflammation by S. aureus nasal carriage and S. aureus enterotoxins in patients and mouse models
JORDE I. 1, GÖRGES S. 1, CAMP B. 1, ASARI A. 1, HOLTFRETER S. 2, WILES S. 3, SCHREIBER J. 1, STEGEMANN-KONISZEWSKI S. 1
1 Department of Pneumology, University Medicine/Otto-von-Guericke University Magdeburg, Magdeburg, Germany; 2 University Medicine Greifswald, Department of Immunology, Greifswald, Germany; 3 The University of Auckland, Institute of Molecular Medicine and Pathology, Auckland, New Zealand
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.