4.7 Article

Staphylococcus aureus internalization in mast cells in nasal polyps: Characterization of interactions and potential mechanisms

Journal

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 145, Issue 1, Pages 147-159

Publisher

MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2019.06.013

Keywords

Chronic rhinosinusitis; chronic rhinosinusitis with nasal polyps; nasal polyps; intracellular bacteria; Staphylococcus aureus; mast cells; bacterial superantigens; staphylococcal enterotoxin B

Funding

  1. Royal College of Surgeons of England
  2. Southampton National Institute for Health Research (NIHR) Respiratory Biomedical Research Centre
  3. NIHR Wellcome Trust Clinical Research Facility
  4. MRC [G0500729] Funding Source: UKRI

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Background: Chronic rhinosinusitis (CRS) with nasal polyps is a common chronic condition. The exact cause of nasal polyps remains unknown. Recently, we made the novel observation of intracellular localization of Staphylococcus aureus within mast cells in nasal polyps. Objective: This follow-up study aimed to further characterize interactions between S aureus and mast cells in this setting and elucidate potential internalization mechanisms with particular emphasis on the role of staphylococcal enterotoxin B (SEB). Methods: A prospective study was performed using an explant tissue model with ex vivo inferior turbinate mucosa obtained from patients with chronic rhinosinusitis with nasal polyps (n = 7) and patients without CRS (n = 5). Immunohistochemistry was used to characterize S aureus uptake into mast cells and investigate the effects of SEB on this process. An in vitro cell-culture model was used to investigate mast cell-S aureus interactions by using a combination of fluorescent in situ hybridization, confocal laser scanning microscopy, scanning electron microscopy, transmission electron microscopy, and proliferation assays. Results: S aureus was captured by extracellular traps and entered mast cells through phagocytosis. Proliferating intracellular S aureus led to the expansion and eventual rupture of mast cells, resulting in release of viable S aureus into the extracellular space. The presence of SEB appeared to promote internalization of S aureus into mast cells. Conclusion: This study provides new insights into the interactions between S aureus and mast cells, including the internalization process, and demonstrates a prominent role for SEB in promoting uptake of the bacteria into these cells.

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