Abstract
The superantigen Staphylococcus aureus (S. aureus) enterotoxin B (SEB) has been proposed a central player in the associations between S. aureus nasal colonization and the development of allergic asthma. Previously, SEB has been shown to aggravate allergic sensitization and allergic airway inflammation (AAI) in experimental mouse models. Aiming at understanding the underlying immunological mechanisms, we tested the hypothesis that intranasal (i.n.) SEB-treatment divergently modulates AAI depending on the timing and intensity of the SEB-encounter. In an ovalbumin-mediated mouse model of AAI, we treated mice i.n. with 50 ng or 500 ng SEB either together with the allergic challenge or prior to the peripheral sensitization. We observed SEB to affect different hallmark parameters of AAI depending on the timing and the dose of treatment. SEB administered i.n. together with the allergic challenge significantly modulated respiratory leukocyte accumulation, intensified lymphocyte activation and, at the higher dose, induced a strong type-1 and pro-inflammatory cytokine response and alleviated airway hyperreactivity in AAI. SEB administered i.n. prior to the allergic sensitization 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. We show a remarkably versatile potential for SEB to either aggravate or alleviate different parameters of allergic sensitization and AAI. Our study thereby not only highlights the complexity of the associations between S. aureus and allergic asthma but possibly even points at prophylactic and therapeutic pathways.
Highlights
Bronchial asthma is a chronic inflammatory condition affecting more than 300 million patients world-wide [1]
Following treatment with 500 ng staphylococcal enterotoxin B (SEB) we observed a significant increase in total cell numbers, CD4+ T cell numbers and eosinophils in the lungs and bronchoalveolar lavage (BAL)
It has been shown that the skin of over 90% of patients with atopic dermatitis is colonized by S. aureus and that disease severity directly correlates to biofilm growth
Summary
Bronchial asthma is a chronic inflammatory condition affecting more than 300 million patients world-wide [1]. Main symptoms are airway hyperreactivity, reversible bronchial obstruction, increased mucus production and structural changes of the airways [2]. With over 60%, allergic asthma represents the most frequent endotype [3]. It is typically characterized by T helper type 2 cell (Th2)-dominated immune responses towards aeroallergens, including the production of allergen specific IgE antibodies, the release of Th2-inflammatory mediators such as interleukin 4 (IL-4), IL-5 and IL-13 as well as the recruitment and activation of mast cells, eosinophils, basophils and others [4, 5]. Major open questions include those of inflammatory endotypes and pre-disposing factors of allergic asthma
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