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Host-microbial interactions in idiopathic pulmonary fibrosis

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Title: Host-microbial interactions in idiopathic pulmonary fibrosis
Authors: Molyneaux, PL
Willis Owen, SA
Cox, MJ
James, P
Cowman, S
Loebinger, M
Blanchard, A
Edwards, LM
Stock, C
Daccord, C
Renzoni, EA
Wells, AU
Moffatt, MF
Cookson, WO
Maher, TM
Item Type: Journal Article
Abstract: RATIONALE: Changes in the respiratory microbiome are associated with disease progression in Idiopathic pulmonary fibrosis (IPF). The role of the host response to the respiratory microbiome however remains unknown. OBJECTIVES: To explore the host-microbial interaction in IPF. METHODS: Sixty patients diagnosed with IPF were prospectively enrolled, together with 20 matched controls. Subjects underwent bronchoalveolar lavage (BAL) and peripheral whole blood was collected into PAXgene tubes for all subjects at baseline. For IPF subjects additional samples were taken at 1, 3, and 6 months and (if alive) a year. Gene expression profiles were generated using Affymetrix Human Gene1.1ST Arrays. MEASUREMENTS AND MAIN RESULTS: Network analysis of gene expression data identified two gene modules that strongly associate with a diagnosis of IPF, BAL bacterial burden (determined by 16S quantitative PCR) and specific microbial OTUs, as well as lavage and peripheral blood neutrophilia. Genes within these modules that are involved in the host defence response include NLRC4, PGLYRP1, MMP9, DEFA4. The modules also contain two genes encoding specific antimicrobial peptides (SLPI and CAMP). Many of these particular transcripts were associated with survival and showed longitudinal over expression in subjects experiencing disease progression, further strengthening their relationship with disease. CONCLUSIONS: Integrated analysis of the host transcriptome and microbial signatures demonstrates an apparent host response to the presence of an altered or more abundant microbiome. These responses remain elevated on longitudinal follow up, suggesting that the bacterial communities of the lower airways may be acting as persistent stimuli for repetitive alveolar injury in IPF.
Issue Date: 13-Jan-2017
Date of Acceptance: 11-Jan-2017
URI: http://hdl.handle.net/10044/1/44257
DOI: https://dx.doi.org/10.1164/rccm.201607-1408OC
ISSN: 1535-4970
Publisher: American Thoracic Society
Start Page: 1640
End Page: 1650
Journal / Book Title: American Journal of Respiratory and Critical Care Medicine
Volume: 195
Issue: 2
Copyright Statement: © 2017 the American Thoracic Society.
Sponsor/Funder: Wellcome Trust
Wellcome Trust
National Institute for Health Research
British Lung Foundation
Funder's Grant Number: 096964/Z/11/Z
097117/Z/11/Z
BRU 6279
BLF-RMF 15-16
Keywords: acute lung injury
expression
idiopathic pulmonary fibrosis
microbiome
usual interstitial pneumonia
Respiratory System
11 Medical And Health Sciences
Publication Status: Published
Conference Place: United States
Appears in Collections:National Heart and Lung Institute
Faculty of Medicine



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