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

Abstract

<h3>Background</h3> 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 <i>Staphylococcus aureus</i>–dominant mucosal biofilms. <h3>Objectives</h3> This study aimed to characterize <i>in vitro</i> grown <i>S aureus</i> biofilm properties in relation to inflammation and CRS severity. The spatial pattern of inflammatory cells in patients' sinonasal tissue was also examined. <h3>Methods</h3> <i>S aureus</i> 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 <i>in vitro</i>, and their metabolic activity, biomass, colony-forming units, and exoprotein production were quantified. <i>S aureus</i> 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 <i>S aureus</i> biofilm properties, the frequency and localization of key immune cells in corresponding sinonasal mucosa, and the disease severity were investigated. <h3>Results</h3> 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 <i>S aureus</i> biofilms showed thicker biomass, higher colony-forming units, and higher exoprotein production than those from controls did (<i>P</i> < .05). <i>S aureus</i> biofilm properties, inflammatory cell numbers, and CRS severity scores were positively correlated. <h3>Conclusions</h3> These findings support the notion of an aberrant immunolocalization of key immune cells in CRSwNP with a critical role of <i>S aureus</i> biofilms in CRS etiopathogenesis.