Staphylococcus aureus impairs sinonasal epithelial repair: effects in CRSwNP and control subjects

Publication date: Available online 20 June 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Fabiana CP. Valera, Manon Ruffin, Damien Adam, Émilie Maillé, Badr Ibrahim, Julie Berube, Simon Rousseau, Emmanuelle Brochiero, Martin Y. Desrosiers
BackgroundThe impact of Staphylococcus aureus (SA) on nasal epithelial repair has never been assessed in chronic rhinosinusitis with nasal polyps (CRSwNP).ObjectiveThis study aimed to determine whether: i) nasal epithelial cell cultures from patients with CRSwNP and control subjects repair differently; ii) SA exoproducts compromise nasal epithelial repair; iii) SA alters lamellipodial dynamics; and iv) deleterious effects could be counteracted by the ROCK inhibitor Y-27632.MethodsPrimary nasal epithelial cells (pNECs), collected during surgeries, were cultured and injured under three conditions: i) basal, ii) exposed to SA exoproducts, and iii) exposed to SA exoproducts and Y-27632. Epithelial repair, lamellipodial dynamics and cytoskeletal organization were assessed.ResultsUnder basal condition, pNECs cultures from CRSwNP presented significantly lower repair rates, and reduced lamellipodial protrusion length and velocity than controls. SA exoproducts significantly decreased repair rates and protrusion dynamics in both controls and CRSwNP, however, the effect of SA on cell protrusions was more sustained over time in CRSwNP. Under basal conditions, immunofluorescence assays showed significantly reduced percentage of cells with lamellipodia at the wound edge in CRSwNP as compared to controls. SA altered cell polarity and decreased the percentage of cells with lamellipodia in both groups. Finally, Y-27632 prevented the deleterious effects of SA exoproducts on CRSwNP repair rates as well as on lamellipodial dynamics and formation.ConclusionsSA exoproducts significantly alter epithelial repair and lamellipodial dynamics on pNECs, this impairment was more pronounced in CRSwNP. Importantly, Y-27632 restored epithelial repair and lamellipodial dynamics in the presence of SA exoproducts.Clinical ImplicationsSinonasal epithelia from CRSwNP exhibit a defect in wound healing compared to controls, which is worsened by exposure to S. aureus. This phenomenon may be prevented by ROCK targeted therapies.

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Teaser

Cells from CRSwNP show a slower repair pattern than controls, both under baseline conditions and following exposure to S. aureus exoproducts. The ROCK inhibitor Y-27632 significantly improves epithelial repair in CRSwNP cells, preventing the deleterious effect of S. aureus.


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