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Recalcitrant CRS is associated with <jats:italic>Staphylococcus aureus<\/jats:italic> dominant mucosal biofilms; however, <jats:italic>S. aureus<\/jats:italic> colonisation of the sinonasal mucosa has also been observed in healthy individuals challenging the significance of <jats:italic>S. aureus<\/jats:italic> in CRS pathogenesis. We aimed to investigate the relationship between CRS key inflammatory markers, <jats:italic>S. aureus<\/jats:italic> biofilm properties\/virulence genes and the severity of the disease. Tissue samples were collected during endoscopic sinus surgery from the ethmoid sinuses of CRS patients with (CRSwNP) and without (CRSsNP) nasal polyps and controls (<jats:italic>n<\/jats:italic>\u2009=\u200959). CD3+ T\u2010cell subset frequencies and key inflammatory markers of CD4+ helper T cells were determined using FACS analysis. Sinonasal <jats:italic>S. aureus<\/jats:italic> clinical isolates were isolated (<jats:italic>n<\/jats:italic>\u2009=\u200926), sequenced and grown into biofilm in vitro, followed by determining their properties, including metabolic activity, biomass, colony\u2010forming units and exoprotein production. Disease severity was assessed using Lund\u2013Mackay radiologic scores, Lund\u2013Kennedy endoscopic scores and SNOT22 quality of life scores. Our results showed that <jats:italic>S. aureus<\/jats:italic> biofilm properties and CRS severity scores correlated positively with total CD4+ T\u2010cell frequencies but looking into CD4+ T\u2010cell subsets showed an inverse correlation with Th1 and Th17 cell frequencies. CD4+ T\u2010cell frequencies were higher in patients harbouring <jats:italic>lukF.PV\u2010<\/jats:italic>positive <jats:italic>S. aureus<\/jats:italic> while its regulatory and Th17 cell subset frequencies were lower in patients carrying <jats:italic>sea\u2212<\/jats:italic> and <jats:italic>sarT\/U\u2010<\/jats:italic>positive <jats:italic>S. aureus.<\/jats:italic> Recalcitrant CRS is characterised by increased <jats:italic>S. aureus<\/jats:italic> biofilm properties in relation to increased total CD4+ helper T\u2010cell frequencies and reduced frequencies of its Th1, Th17 and regulatory T\u2010cell subsets. These findings offer insights into the pathophysiology of CRS and could lead to the development of more targeted therapies.<\/jats:p>","DOI":"10.1111\/imm.13655","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T13:28:48Z","timestamp":1684243728000},"page":"120-133","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["<i>Staphylococcus aureus<\/i> biofilm properties and chronic rhinosinusitis severity scores correlate positively with total <scp>CD4<\/scp>+ <scp>T\u2010<\/scp>cell frequencies and inversely with its Th1, Th17 and regulatory cell frequencies"],"prefix":"10.1111","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9822-5392","authenticated-orcid":false,"given":"Gohar","family":"Shaghayegh","sequence":"first","affiliation":[{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences The University of Adelaide  Adelaide Australia"},{"name":"The Department of Surgery\u2010Otolaryngology, Head and Neck Surgery University of Adelaide  Adelaide Australia"},{"name":"The Department of Surgery\u2010Otolaryngology, Head and Neck Surgery The Basil Hetzel Institute for Translational Health Research  Woodville South Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3109-4540","authenticated-orcid":false,"given":"Clare","family":"Cooksley","sequence":"additional","affiliation":[{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences The University of Adelaide  Adelaide Australia"},{"name":"The Department of Surgery\u2010Otolaryngology, Head and Neck Surgery University of Adelaide  Adelaide Australia"},{"name":"The Department of Surgery\u2010Otolaryngology, Head and Neck Surgery The Basil Hetzel Institute for Translational Health Research  Woodville South Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5885-4186","authenticated-orcid":false,"given":"George","family":"Bouras","sequence":"additional","affiliation":[{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences The University of Adelaide  Adelaide Australia"},{"name":"The Department of Surgery\u2010Otolaryngology, Head and Neck Surgery University of Adelaide  Adelaide Australia"},{"name":"The Department of Surgery\u2010Otolaryngology, Head and Neck Surgery The Basil Hetzel Institute for Translational Health Research  Woodville South Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5469-3397","authenticated-orcid":false,"given":"Roshan","family":"Nepal","sequence":"additional","affiliation":[{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences The University of Adelaide  Adelaide Australia"},{"name":"The Department of Surgery\u2010Otolaryngology, Head and Neck Surgery University of Adelaide  Adelaide Australia"},{"name":"The Department of Surgery\u2010Otolaryngology, Head and Neck Surgery The Basil Hetzel Institute for Translational Health Research  Woodville South Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6692-9478","authenticated-orcid":false,"given":"Ghais","family":"Houtak","sequence":"additional","affiliation":[{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences The University of Adelaide  Adelaide Australia"},{"name":"The Department of Surgery\u2010Otolaryngology, Head and Neck Surgery University of Adelaide  Adelaide Australia"},{"name":"The Department of Surgery\u2010Otolaryngology, Head and Neck Surgery The Basil Hetzel Institute for Translational Health Research  Woodville South 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Department of Surgery\u2010Otolaryngology, Head and Neck Surgery University of Adelaide  Adelaide Australia"},{"name":"The Department of Surgery\u2010Otolaryngology, Head and Neck Surgery The Basil Hetzel Institute for Translational Health Research  Woodville South Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2967-1855","authenticated-orcid":false,"given":"Alkis James","family":"Psaltis","sequence":"additional","affiliation":[{"name":"Adelaide Medical School, Faculty of Health and Medical Sciences The University of Adelaide  Adelaide Australia"},{"name":"The Department of Surgery\u2010Otolaryngology, Head and Neck Surgery University of Adelaide  Adelaide Australia"},{"name":"The Department of Surgery\u2010Otolaryngology, Head and Neck Surgery The Basil Hetzel Institute for Translational Health Research  Woodville South 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