Intranasal staphylococcal enterotoxin B (SEB) modulates allergic airway inflammation in a time- and dose-dependent manner in a mouse model

Allergic asthma is a particularly heterogeneous chronic inflammatory condition of the airways and its predisposing as well as modulating factors are of special interest with respect to prophylaxis and treatment. Correlations between nasal colonization with Staphylococcus aureus (S. aureus) and allergic asthma have been recognized, but on a mechanistic basis remain elusive. S. aureus is capable of producing a variety of toxins that act as superantigens mediating strong unspecific T cell activation. Particularly S. aureus enterotoxin B (SEB) has been proposed a central player in the interplay between S. aureus and allergic asthma and has been shown to aggravate allergic sensitization and allergic airway inflammation (AAI) in experimental mouse models.

Using a mouse model (C57BL/6) based on an airway antigen challenge following peripheral sensitization, we are seeking mechanistic insights into how SEB modulates AAI. We analyzed the effects of intranasal treatment with a low and a high dose of SEB before sensitization or together with the allergic challenge. We assessed the recruitment of leukocytes to the respiratory tract, cytokine production, allergen specific IgE levels and airway hyperreactivity. SEB affected different hallmark parameters of AAI depending on the timing and the dose of administration. Together with the allergic challenge, SEB significantly modulated respiratory leukocyte accumulation and intensified lymphocyte activation. At the higher dose, SEB together with the allergic challenge induced a strong type-1 and pro-inflammatory cytokine response and significantly alleviated airway hyperreactivity. If administered prior to sensitization, SEB at the lower dose significantly boosted the specific IgE response while administration of the higher dose led to a significantly reduced recruitment of immune cells, including eosinophils, to the respiratory tract and to a significantly dampened Th-2 cytokine response without inducing a Th-1 or pro-inflammatory response.

Our results show a remarkably versatile potential for SEB to either aggravate or alleviate different parameters of allergic sensitization and airway inflammation. Thereby, our study underlines the high complexity of the associations between S. aureus and allergic asthma and possibly even points at beneficial effects.

 

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Artikel online veröffentlicht:
11. Mai 2022