Staphylococcus aureus is a frequent colonizer of the upper and lower airways and the skin. In the nose, it may form biofilms and resides intramucosally, and has been associated with different types of T helper cell reactions; recently, arguments for a role also in Th2 immune diseases such as chronic rhinosinusitis and asthma accumulate [
24].
S. aureus forms a rich immune proteome, with more than 1500 different proteins comprising virulence factors, enterotoxins including classical superantigens, and proteins with enzymatic properties. Whereas the classical enterotoxins may activate T cell populations unspecifically via the variable ß-chain of T cell receptors, other recently discovered molecules such as serine protease-like proteins (spls) obviously elicit a strong Th2-biased immune response and act as allergens or super-allergens, as they induce IgE formation also to inert proteins [
25]. Spl-specific memory T cells elaborate Th2 cytokines including IL-4, IL-5 and IL-13, whereas small amounts of IFN-γ, IL-6, TNF and IL-17 are produced. IL-4 and IL-13 drive the immunoglobulin class switch to IgE, and IL-5 orchestrates activation and survival of eosinophils. Both protein families, enterotoxins and spls, have been found in human airway mucosa, and elicit, when given intra-tracheal in mice, an allergic lung inflammation. A typical hallmark of Th2 reactions is the formation of IgE; in the presence of
staphylococcal superantigens, a polyclonal IgE formation is regularly found including several IgE antibodies directed towards classical and ECG-locus enterotoxins (SE-IgEs); the latter are indicators of a manifest immune reaction to
S. aureus products. SE-IgE was significantly associated with asthma in 3000 Europeans [
26] and was shown to be linked to severe asthma, atopic or non-atopic, both in European [
27] and Asian populations [
28]. MeDALL (Mechanisms of the Development of Allergy) proposed that
S. aureus sensitization was associated with a re-occurrence of foetal Type 2 signalling leading to the onset of IgE and non-IgE dependent diseases [
29,
30].