Imperial College London

ProfessorSebastianJohnston

Faculty of MedicineNational Heart & Lung Institute

Asthma UK Clinical Chair
 
 
 
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Contact

 

+44 (0)20 7594 3764s.johnston

 
 
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Assistant

 

Mr Christophe Tytgat +44 (0)20 7594 3849

 
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Location

 

343Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lan:2018:10.1016/j.jaci.2018.09.041,
author = {Lan, F and Zhong, H and Zhang, N and Johnston, SL and Wen, W and Papadopoulos, N and Zhang, L and Bachert, C},
doi = {10.1016/j.jaci.2018.09.041},
journal = {J Allergy Clin Immunol},
title = {IFN-λ1 enhances Staphylococcus aureus clearance in healthy nasal mucosa but not in nasal polyps.},
url = {http://dx.doi.org/10.1016/j.jaci.2018.09.041},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by TH2-skewed inflammation and increased colonization by Staphylococcus aureus. IFN-λ1 is known for its antiviral activity, but there is little information on its antibacterial role. OBJECTIVE: We sought to determine the expression and release of IFN-λ1 from nasal mucosal tissue of healthy subjects and patients with CRSwNP on exposure to S aureus and assess its potential role in antibacterial defense mechanisms. METHODS: Nasal tissue from healthy subjects and patients with CRSwNP was exposed to S aureus, and we assessed expression of IFN-λ1, 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 and intracellular reactive oxidase substrate (ROS), the IFN-λ1 receptor IL-28 receptor (IL-28R), and the Janus kinase/signal transducer and activator of transcription (STAT) 1 pathway by means of immunofluorescence staining. RESULTS: S aureus infection increased IFN-λ1 expression in tissue from patients with CRSwNP. IFN-λ1 (10 ng/mL) significantly decreased the number of S aureus colony-forming units in healthy control tissue but not in tissue from patients with CRSwNP and upregulated MUC5AC and MUC5B expression in control tissue on S aureus infection. IFN-λ1 stimulation increased intracellular killing of S aureus in THP1-derived macrophages and substantially increased lysosomal-associated membrane protein 1, 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 clearance of S aureus in healthy nasal mucosa and enhances antibacterial function of macrophages through IFN-λ1-IL-28R-ROS-Janus kinase-STAT signaling pathways.
AU - Lan,F
AU - Zhong,H
AU - Zhang,N
AU - Johnston,SL
AU - Wen,W
AU - Papadopoulos,N
AU - Zhang,L
AU - Bachert,C
DO - 10.1016/j.jaci.2018.09.041
PY - 2018///
TI - IFN-λ1 enhances Staphylococcus aureus clearance in healthy nasal mucosa but not in nasal polyps.
T2 - J Allergy Clin Immunol
UR - http://dx.doi.org/10.1016/j.jaci.2018.09.041
UR - https://www.ncbi.nlm.nih.gov/pubmed/30508540
ER -