Colonized S. aureus may release various IgE-reactive enzymes and toxins, including staphylococcal enterotoxins (SEs), serine protease-like proteins, and fibronectin-binding protein [4]. Elevated colonization rates correlate with increased IgE formation against SEs in patients with chronic airway diseases, such as chronic rhinosinusitis and asthma, compared to healthy individuals.

SE-IgE sensitization, defined as a high serum level of SEIgE, plays a significant role in the pathogenesis of asthma, chronic rhinosinusitis, and atopic dermatitis [5]. SE-IgE sensitization is associated with severe asthma, increased risk of severe exacerbations, and eosinophilic inflammation. S. aureus induces SE-IgE-sensitized eosinophilic inflammation through multiple mechanisms [6]. The bacterium releases δ-toxin, damaging epithelial barriers and facilitating allergen penetration. SE and other superantigens induce excessive release of Th2 cytokines, including interleukin-4 (IL-4), IL-5, and IL-13, from tissue T cells. Recent studies have reported eosinophilic migration through the human airway epithelium in response to S. aureus exposure, resulting in eosinophil extracellular trap formation and persistent inflammatory responses. IL-5-activated eosinophils can be recruited by S. aureus to further degrade the epithelium by inducing the release of major basic proteins, the epithelial-toxic components of the eosinophil extracellular trap.

SEs and other T cell superantigens are exceptionally stable and significantly influence the immune system. They can circumvent the T cells’ requirement for antigen recognition by directly crosslinking T cell receptors with major histocompatibility complex class II molecules, leading to the polyclonal activation of T cells, including T helper-2 cells, regardless of their antigen specificity. S. aureus can secrete staphylococcal protein A, which acts as a B cell superantigen to induce mast cell degranulation [6].

Based on these findings, several studies have examined the associations between S. aureus colonization and asthma. A meta-analysis in Korea reported a significant association between nasal S. aureus colonization and adult asthma (odds ratio: 1.19; 95% confidence interval: 1.06–1.34; I2 = 1%) [7]. Investigating asthma severity, Caruso et al. [8] reported that SE-B-specific IgE was associated with chronic rhinosinusitis with or without nasal polyps in severe asthma. However, there was no correlation between SE-B-specific antigens and eosinophilia, severity, or steroid dosage. Several recent studies have focused on S. aureus enterotoxins and asthma severity, particularly airflow limitations. Schleich et al. [9] demonstrated that asthma patients sensitized to SEs had later disease onset, higher incidence of exacerbations and nasal polyps, and more severe airway obstruction. They also had higher fractional exhaled nitric oxide and sputum concentrations of IgE and IL-5. Won et al. [10] recently reported a 2-year follow-up study that demonstrated correlations among SE-IgE sensitization, asthma exacerbations, and fixed airflow limitation in elderly asthmatics, which suggested that SE-IgE sensitization may mediate airway remodeling.

A study by Sim et al. [11] in the current issue of the Korean Journal of Internal Medicine found that high SE-B-specific IgE levels correlated strongly with eosinophilic activation markers, including eosinophil cationic protein and eosinophil-derived neurotoxin. This supports the possibility that SE-B-specific IgE sensitization might be associated with the pathogenesis of eosinophilic asthma. This study contributes to a deeper understanding of the asthma phenotype through the association of S. aureus sensitization with eosinophilic inflammation.

In conclusion, S. aureus plays a prominent role in orchestrating severe airway inflammation in asthma.