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Σάββατο 8 Δεκεμβρίου 2018

Interferon-lambda1 enhances Staphylococcus aureus clearance in healthy nasal mucosa, not in nasal polyps.

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Interferon-lambda1 enhances Staphylococcus aureus clearance in healthy nasal mucosa, not in nasal polyps.

J Allergy Clin Immunol. 2018 Nov 30;:

Authors: Lan F, Zhong H, Zhang N, Johnston SL, Wen W, Papadopoulos N, Zhang L, Bachert C

Abstract
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a Th2-skewed inflammation and an increased colonization by Staphylococcus aureus (S. aureus). Interferon-lambda 1(IFN-λ1) is known for its antiviral activity, there is little information on its anti-bacterial role.
OBJECTIVE: To determine the expression and release of IFN-λ1 from healthy and CRSwNP nasal mucosal tissue upon exposure to S. aureus and assess its potential role in anti-bacterial defense mechanisms.
METHODS: Healthy and CRSwNP nasal tissues were exposed to S. aureus and assessed the expression of IFN-λ1 and MUC5AC and MUC5B. THP1 derived macrophages incubated with or without IFN-λ1 were assessed for uptake and killing of S. aureus and expression of lysosomal-associated membrane protein 1 (LAMP1) and intracellular reactive oxidase substrate (ROS), IFN-λ1 receptor IL-28R and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) 1 pathway by immunofluorescence staining.
RESULTS: S. aureus infection increased IFN-λ1 expression in healthy nasal tissue, not in CRSwNP tissue. IFN-λ1 (10 ng/ml) significantly decreased the number of S. aureus colony-forming units in healthy control tissue, but not in CRSwNP tissue, and upregulated MUC5AC and MUC5B expression in control tissues upon S. aureus infection. IFN-λ1 stimulation increased intracellular killing of S. aureus in THP1 derived macrophages and substantially increased LAMP1, IL-28R, ROS and STAT signaling in macrophages incubated with S. aureus. All of these effects were attenuated by blocking IL-28R and ROS activities.
CONCLUSIONS: IFN-λ1 favors the clearance of S. aureus in healthy nasal mucosa, and enhances antibacterial function of macrophages via IFN-λ1-IL-28R-ROS-JAK-STAT signaling pathways.

PMID: 30508540 [PubMed - as supplied by publisher]



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