Publication date: Available online 30 November 2018
Source: Journal of Allergy and Clinical Immunology
Author(s): Feng Lan, Hua Zhong, Nan Zhang, Sebastian L. Johnston, Weiping Wen, Nikos Papadopoulos, Luo Zhang, Claus Bachert
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.
from Allergy and Immunology via a.sfakia on Inoreader https://ift.tt/2BIGUsb
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