Abstract
While immunoglobulin (Ig) 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 with 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. Staphylococcus aureus manipulates the airway mucosal immunology at various levels via its proteins, including superantigens, serine-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 T helper (Th) 2 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.
Abstract
Late-onset non-atopic, often severe asthma is not well understood. There is increasing evidence that bacteria and their proteins, specifically S. aureus and its superantigens and serine protease-like proteins may represent the triggers we are looking for. http://bit.ly/386oP4G
Footnotes
Conflict of interest: C. Bachert has nothing to disclose.
Conflict of interest: M. Humbert reports personal fees from AstraZeneca, GSK, Merck, Novartis, Roche, Sanofi and Teva, outside the submitted work.
Conflict of interest: N.A. Hanania 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 and AstraZeneca.
Conflict of interest: N. Zhang has nothing to disclose.
Conflict of interest: S. Holgate has nothing to disclose.
Conflict of interest: R. Buhl has nothing to disclose.
Conflict of interest: B.M. Bröker has nothing to disclose.
Support statement: C. Bachert: this work was supported by FWO Flanders, EOS project GOG2318N, and grants from FWO Flanders (G065319N, 1506218N, 1507118N, G051918N, G065319N 1515516N, 1841713N, G.039412N, G.067512N and FWO/PDO/108), the Interuniversity Attraction Poles Grant P7/30, from Ghent University BOF 14-GOA-019 and BOF 01/03618, and the European Commission's Seventh Framework Programme number 260895 (PREDICTA). B.M. Bröker: this work was supported by the German Research Foundation (CRC-TRR 34, RTG 1870), the Federal Ministry of Research and Education (InfectControl 2020), the EU (IMI-Combacte) as well as the State of Mecklenburg Western Pomerania and the European Social Fund (ESF; Card-ii-Omics, KoInfekt). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received August 19, 2019.
- Accepted December 31, 2019.
- Copyright ©ERS 2020