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Staphylococcus aureus internalisation in mast cells in nasal polyps - characterisation of interactions and potential mechanisms

Staphylococcus aureus internalisation in mast cells in nasal polyps - characterisation of interactions and potential mechanisms
Staphylococcus aureus internalisation in mast cells in nasal polyps - characterisation of interactions and potential mechanisms
Background
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic condition. The exact cause of nasal polyps remains unknown. Recently, we made the novel observation of intracellular localisation of Staphylococcus aureus (S aureus) within mast cells in nasal polyps.

Objective
This follow-up study aimed to further characterise interactions between S aureus and mast cells in this setting, and elucidate potential internalisation mechanisms with particular emphasis on the role of S aureus enterotoxin B (SEB).

Methods
A prospective study was performed using an explant tissue model with ex vivo inferior turbinate mucosa obtained from CRSwNP patients (n=7) and non-CRS (n=5) patients. Immunohistochemistry was used to characterise 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 using a combination of fluorescent in situ hybridisation, confocal laser scanning microscopy, scanning electron microscopy, transmission electron microscopy, and proliferation assays.

Results
S aureus were entrapped 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 internalisation of S aureus into mast cells.

ConclusionThis study provides new insights into the interactions between S aureus and mast cells, including the internalisation process, and demonstrates a prominent role for SEB in promoting uptake of the bacteria into these cells.
Chronic rhinosinusitis, chronic rhinosinusitis with nasal polyps, nasal polyps, intracellular bacteria, Staphylococcus aureus, mast cells, bacterial superantigens, SEB
0091-6749
Hayes, Stephen
7c6543a2-17a4-4629-91bb-bb64965df66a
Biggs, Timothy Charles
887596b4-f2ad-4067-8f01-5f2cfe1ae394
Goldie, Simon Patrick
0bf2f8c9-290b-403f-bf52-5602708810e9
Harries, Philip G.
df33be64-b580-4fdf-ac4d-4c842b55d753
Walls, Andrew
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Allan, Raymond
390a7d0a-38e1-410a-8dfe-c8ef8408f5e1
Pender, Sylvia
62528b03-ec42-41bb-80fe-48454c2c5242
Salib, Rami
d6fde1c1-5b5e-43f7-ae1c-42cce6a0c9fc
Hayes, Stephen
7c6543a2-17a4-4629-91bb-bb64965df66a
Biggs, Timothy Charles
887596b4-f2ad-4067-8f01-5f2cfe1ae394
Goldie, Simon Patrick
0bf2f8c9-290b-403f-bf52-5602708810e9
Harries, Philip G.
df33be64-b580-4fdf-ac4d-4c842b55d753
Walls, Andrew
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Allan, Raymond
390a7d0a-38e1-410a-8dfe-c8ef8408f5e1
Pender, Sylvia
62528b03-ec42-41bb-80fe-48454c2c5242
Salib, Rami
d6fde1c1-5b5e-43f7-ae1c-42cce6a0c9fc

Hayes, Stephen, Biggs, Timothy Charles, Goldie, Simon Patrick, Harries, Philip G., Walls, Andrew, Allan, Raymond, Pender, Sylvia and Salib, Rami (2019) Staphylococcus aureus internalisation in mast cells in nasal polyps - characterisation of interactions and potential mechanisms. Journal of Allergy and Clinical Immunology. (doi:10.1016/j.jaci.2019.06.013).

Record type: Article

Abstract

Background
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic condition. The exact cause of nasal polyps remains unknown. Recently, we made the novel observation of intracellular localisation of Staphylococcus aureus (S aureus) within mast cells in nasal polyps.

Objective
This follow-up study aimed to further characterise interactions between S aureus and mast cells in this setting, and elucidate potential internalisation mechanisms with particular emphasis on the role of S aureus enterotoxin B (SEB).

Methods
A prospective study was performed using an explant tissue model with ex vivo inferior turbinate mucosa obtained from CRSwNP patients (n=7) and non-CRS (n=5) patients. Immunohistochemistry was used to characterise 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 using a combination of fluorescent in situ hybridisation, confocal laser scanning microscopy, scanning electron microscopy, transmission electron microscopy, and proliferation assays.

Results
S aureus were entrapped 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 internalisation of S aureus into mast cells.

ConclusionThis study provides new insights into the interactions between S aureus and mast cells, including the internalisation process, and demonstrates a prominent role for SEB in promoting uptake of the bacteria into these cells.

Text
FINAL Manuscript UNMARKED - Accepted Manuscript
Restricted to Repository staff only until 26 June 2020.
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More information

Accepted/In Press date: 4 June 2019
e-pub ahead of print date: 27 June 2019
Keywords: Chronic rhinosinusitis, chronic rhinosinusitis with nasal polyps, nasal polyps, intracellular bacteria, Staphylococcus aureus, mast cells, bacterial superantigens, SEB

Identifiers

Local EPrints ID: 432078
URI: https://eprints.soton.ac.uk/id/eprint/432078
ISSN: 0091-6749
PURE UUID: 64c88634-7319-4447-9ed9-597eed18277d
ORCID for Sylvia Pender: ORCID iD orcid.org/0000-0001-6332-0333
ORCID for Rami Salib: ORCID iD orcid.org/0000-0002-6753-7844

Catalogue record

Date deposited: 01 Jul 2019 16:30
Last modified: 10 Dec 2019 01:48

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