Impaired Functions of Macrophage from Cystic Fibrosis Patients: CD11b, TLR-5 Decrease and sCD14, Inflammatory Cytokines Increase

作者: Karin Simonin-Le Jeune , André Le Jeune , Stéphane Jouneau , Chantal Belleguic , Pierre-François Roux

DOI: 10.1371/JOURNAL.PONE.0075667

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摘要: BackgroundEarly in life, cystic fibrosis (CF) patients are infected with microorganisms. The role of macrophages has largely been underestimated literature, whereas the focus being mostly on neutrophils and epithelial cells. Macrophages may however play a significant initiating stages this disease, via an inability to act as suppressor cell. Yet macrophage dysfunction be first step cascade events leading chronic inflammation/infection CF. Moreover, reports have suggested that CFTR contribute altered inflammatory response CF by modification normal functions. ObjectivesIn order highlight possible intrinsic defects due impaired CFTR, we studied cytokines secretions, recognition pathogens phagocytosis peripheral blood monocyte-derived from stable adult healthy subjects (non-CF). ResultsIn supernatants, concentrations sCD14, IL-1β, IL-6, TNF-α IL-10 were strongly raised. Furthermore expression CD11b TLR-5 sorely decreased macrophages. Beside, no difference was observed for mCD14, CD16, CD64, TLR-4 TLR1/TLR-2 expressions. strong inhibition Elsewhere non-CF also led alterations function well expression. ConclusionsAltogether, these findings demonstrate excessive inflammation macrophages, characterized overproduction sCD14 cytokines, TLR-5, phagocytosis. This leads clearance non-resolution infection thereby inducing exaggerated pro-inflammatory response.

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