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Chronic rhinosinusitis patients display an aberrant immune cell localization with enhanced S aureus biofilm metabolic activity and biomass - 03/03/23

Doi : 10.1016/j.jaci.2022.08.031 
Gohar Shaghayegh, PhD a, b, Clare Cooksley, PhD a, b, George Spyro Bouras, BSc a, b, Beula Subashini Panchatcharam, MD, PhD a, b, Rejhan Idrizi, PhD c, d, Metta Jana, PhD c, d, Sarah Ellis, PhD c, d, Alkis James Psaltis, MD, PhD a, b, Peter-John Wormald, MD a, b, Sarah Vreugde, MD, PhD a, b,
a Department of Surgery—Otolaryngology, Head and Neck Surgery, University of Adelaide, Australia 
b Central Adelaide Local Health Network, The Queen Elizabeth Hospital, Woodville South, Australia 
c Peter MacCallum Cancer Centre, Melbourne, Australia 
d Sir Peter MacCallum Department of Oncology, The University of Melbourne, Australia 

Corresponding author: Sarah Vreugde, MD, PhD, Department of Surgery—Otolaryngology, Head and Neck Surgery, University of Adelaide, Adelaide, South Australia, Australia.Department of Surgery—OtolaryngologyHead and Neck SurgeryUniversity of AdelaideAdelaideSouth AustraliaAustralia

Graphical abstract




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Abstract

Background

Chronic rhinosinusitis (CRS) is a persistent inflammation of the sinus mucosa associated with dysfunction of the sinuses’ natural defense mechanism and induction of different inflammatory clusters. Severe recalcitrant CRS is unresponsive to medical and surgical interventions and often has Staphylococcus aureus–dominant mucosal biofilms.

Objectives

This study aimed to characterize in vitro grown S aureus biofilm properties in relation to inflammation and CRS severity. The spatial pattern of inflammatory cells in patients’ sinonasal tissue was also examined.

Methods

S aureus isolated from the nasal swabs of patients with CRS with nasal polyps (CRSwNP), those with CRS without nasal polyps, and controls (n = 72) were grown into biofilm in vitro, and their metabolic activity, biomass, colony-forming units, and exoprotein production were quantified. S aureus virulence genes were evaluated using whole-genome sequencing. Patients’ matched sinonasal tissue blocks (n = 57) were analyzed using Opal multiplex immunostaining, and their disease severity was determined using the Lund-Mackay computed tomography score. Correlations among S aureus biofilm properties, the frequency and localization of key immune cells in corresponding sinonasal mucosa, and the disease severity were investigated.

Results

Increased infiltration of CD3+, CD68+, CD20+, and CD138+ cells was observed in tissue of patients with CRSwNP compared to tissue from controls. CD3+, CD138+, and MBP+ cells diffused deeper into the tissue in CRSwNP but clustered close to the epithelium in controls. This study also found CRSwNP–derived S aureus biofilms showed thicker biomass, higher colony-forming units, and higher exoprotein production than those from controls did (P < .05). S aureus biofilm properties, inflammatory cell numbers, and CRS severity scores were positively correlated.

Conclusions

These findings support the notion of an aberrant immunolocalization of key immune cells in CRSwNP with a critical role of S aureus biofilms in CRS etiopathogenesis.

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Key words : S aureus biofilm, inflammatory cells, disease severity, sinonasal mucosa, chronic rhinosinusitis

Abbreviations used : CFU, CRS, CRSsNP, CRSwNP, CT, DAPI, EPOS, FFPE, ica, MBP, MLST, MRSA, TSA


Plan


 This study was supported by The Hospital Research Foundation Postgraduate Research Scholarship (to G.S.) and The University of Adelaide scholarship (to G.S.). This work was supported by an National Health and Medical Research Council grant APP1196832 to P.J.W.
 Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interests.


© 2022  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 151 - N° 3

P. 723 - mars 2023 Retour au numéro
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