Modulation of Allergic Sensitization and Allergic Inflammation by Staphylococcus aureus Enterotoxin B in an Ovalbumin Mouse Model

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.

Resolved Influenza A Virus Infection Has Extended Effects on Lung Homeostasis and Attenuates Allergic Airway Inflammation in a Mouse Model

“…Flow cytometry was performed as described [37]. Briefly, cells were incubated with anti-CD16/CD36 (2.4G2) to block Fc-receptors and were stained with fixable live/dead stain (BioLegend).…”

“…Assessment of airway hyperreactivity was performed as described [37]. Anesthetized and tracheotomized mice were mechanically ventilated (Buxco FinePointe R/C, DSI TM USA) and after 5 min of acclimation, 10 µL PBS containing increasing concentrations of methacholine (0, 6.25, 12.5, 25, 50 mg/mL) were nebulized into the breathing air (delivery duration 20 s).…”

“…Histopathological analyses were performed as described [37]. Whole lungs were fixed in 4% formalin and embedded in paraffin.…”

Potent Anti-Inflammatory Effects of Tetracyclines on Human Eosinophils

“…There's some debate on the role of antibiotic therapy in the treatment of allergic disorders with concomitant bacterial infections (42,43). Although antibiotic treatment has different outcomes in asthma, chronic rhinitis, and nasal polyposis, the impact of S. aureus enterotoxins in allergic diseases is increasing (44)(45)(46)(47)(48)(49)(50)(51)(52). Staphylococcus aureus enterotoxins are thought to act as superantigens, inducing production of polyclonal IgE via Bcell and T-cell activation, and triggering release of inflammatory mediators (50).…”

Infection-Associated Mechanisms of Neuro-Inflammation and Neuro-Immune Crosstalk in Chronic Respiratory Diseases

“…Various studies suggest that exposure to S. aureus and its associated enterotoxins is a risk factor for the development of allergic asthma [ 125 ]. Experimentally, we recently showed that intranasally administered S. aureus enterotoxin B harbors a versatile potential to modulate allergic airway inflammation [ 126 ]. During S. aureus lung infection, nociceptors regulate protective immunity through CGRP release via the transient receptor potential ion channel 1 (TRPV1).…”