Staphylococcus aureus lysate induces an IgE response via memory B cells in nasal polyps.

BACKGROUND:Locally increased IgE levels plays a pathologic role in chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE:This study aimed to investigate whether Staphylococcus aureus could induce aberrant IgE synthesis in CRSwNP and the potential mechanisms involved. METHODS:Total IgE, IL-4, IL-5, and IL-13 concentrations in the supernatants of the cultures stimulated with S aureus lysate were assessed by ELISA. S aureus-induced cellular responses were investigated by single-cell RNA sequencing. Flow cytometry and quantitative reverse transcription PCR were used to analyze B-cell subsets and stimulated cell ε-germline transcript expression, respectively. IgE-positive B-cell and germinal center localization were assessed by immunohistochemistry and immunofluorescence. RESULTS:S aureus lysate induced IgE production in the supernatants of nasal polyp (NP) tissues but not in those of healthy nasal mucosa. Moreover, IgE levels increased from days 2 to 4 after stimulation, paralleling the enhanced ε-germline transcript, IL-5, and IL-13 expression. Single-cell RNA sequencing revealed that there were increased IL-5 and IL-13 in group 2 innate lymphoid cells and identified a clonal overlap between unstimulated memory B cells and S aureus-stimulated plasma cells. The enriched IgE within NPs was mainly produced by IgE-negative memory B cells. Cellular evidence indicated that the IgE memory response to S aureus might also exist in the peripheral blood of CRSwNP patients. The S aureus-induced IgE memory response was associated with elevated IgE levels in NPs, asthma, and postoperative CRSwNP recurrence. CONCLUSIONS:S aureus induced an IgE response via IgE-negative memory B cells in CRSwNP patients, possibly contributing to CRSwNP development.