While immunoglobulin E is a prominent biomarker for early-onset, its levels are often elevated in non-allergic late-onset asthma. However, the pattern of IgE expression in the latter is mostly polyclonal, with specific IgEs low or below detection level albeit an increased total IgE. In late-onset severe asthma patients, specific IgE to Staphylococcal enterotoxins (se-IgE) can frequently be detected in serum, and has been associated with asthma, with severe asthma defined by hospitalisations, oral steroid use and decrease in lung function. Recently, se-IgE was demonstrated to even predict the development into severe asthma with exacerbations over the next decade. S. aureus manipulates the airway mucosal immunology at various levels via its proteins, including superantigens, serin-protease-like proteins (spls), or protein A (SpA) and possibly others. Release of IL-33 from respiratory epithelium and activation of innate lymphoid cells (ILCs) via its receptor ST2, type 2 cytokine release from those ILCs and TH2 cells, mast cell degranulation, massive local B-cell activation and IgE formation, and finally eosinophil attraction with consequent release of extracellular traps, adding to the epithelial damage and contributing to disease persistence via formation of Charcot-Leyden crystals are the most prominent hallmarks of the manipulation of the mucosal immunity by S. aureus. In summary, S. aureus claims a prominent role in the orchestration of severe airway inflammation and in current and future disease severity. In this review, we discuss current knowledge in this field and outline the needs for future research to fully understand the impact of S. aureus and its proteins on asthma.
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Conflict of interest: Dr. Bachert has nothing to disclose.
Conflict of interest: Dr. Humbert reports personal fees from Astrazeneca, personal fees from GSK, personal fees from Merck, personal fees from Novartis, personal fees from Roche, personal fees from Sanofi, personal fees from Teva, outside the submitted work.
Conflict of interest: NAH has received honoraria for serving on advisory boards or as consultant from Novartis, Genentech, Roche, Novartis, AstraZeneca, GSK, Gossamer Bio and Boehringer Ingelheim. His institution received research grant support on his behalf from GSK, Boehringer Ingelheim, AstraZeneca
Conflict of interest: Dr. Zhang has nothing to disclose.
Conflict of interest: Dr. holgate has nothing to disclose.
Conflict of interest: Dr. Buhl has nothing to disclose.
Conflict of interest: Dr. Bröker has nothing to disclose.