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 epsilon-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 epsilon-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. (J Allergy Clin Immunol 2024;153:718-31.)