Host–Microbial Interactions in Idiopathic Pulmonary Fibrosis
| Autor: | Phillip James, Athol U. Wells, Saffron A.G. Willis-Owen, Michael J. Cox, Steven Cowman, Andrew D Blanchard, Carmel Stock, Cécile Daccord, Toby M. Maher, Michael R. Loebinger, William O.C.M. Cookson, Miriam F. Moffatt, Elisabetta A. Renzoni, Lindsay M. Edwards, Philip L. Molyneaux |
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| Přispěvatelé: | British Lung Foundation, Wellcome Trust, National Institute for Health Research, Medical Research Council (MRC) |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Respiratory System PATHOGENESIS microbiome MUC5B PROMOTER POLYMORPHISM SUSCEPTIBILITY Critical Care and Intensive Care Medicine DISEASE Idiopathic pulmonary fibrosis 0302 clinical medicine Usual interstitial pneumonia Medicine Prospective Studies usual interstitial pneumonia Respiratory system skin and connective tissue diseases PHOSPHORYLATION Prospective cohort study 11 Medical and Health Sciences Whole blood medicine.diagnostic_test Microbiota ASSOCIATION respiratory system idiopathic pulmonary fibrosis NETWORKS FACTOR-KAPPA-B Real-time polymerase chain reaction Host-Pathogen Interactions Female Life Sciences & Biomedicine Bronchoalveolar Lavage Fluid Pulmonary and Respiratory Medicine 03 medical and health sciences Critical Care Medicine General & Internal Medicine expression Humans Microbiome Aged Science & Technology business.industry Original Articles medicine.disease respiratory tract diseases 030104 developmental biology Bronchoalveolar lavage acute lung injury 030228 respiratory system EXACERBATION Immunology Microbial Interactions sense organs Transcriptome business LUNG INJURY Follow-Up Studies |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine. 195:1640-1650 |
| ISSN: | 1535-4970 1073-449X |
| DOI: | 10.1164/rccm.201607-1408oc |
| Popis: | 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 remains unknown.To explore the host-microbial interactions in IPF.Sixty patients diagnosed with IPF were prospectively enrolled together with 20 matched control subjects. Subjects underwent bronchoalveolar lavage (BAL), and peripheral whole blood was collected into PAXgene tubes for all subjects at baseline. For subjects with IPF, additional samples were taken at 1, 3, and 6 months and (if alive) 1 year. Gene expression profiles were generated using Affymetrix Human Gene 1.1 ST arrays.By network analysis of gene expression data, we identified two gene modules that strongly associated with a diagnosis of IPF, BAL bacterial burden (determined by 16S quantitative polymerase chain reaction), and specific microbial operational taxonomic units, as well as with lavage and peripheral blood neutrophilia. Genes within these modules that are involved in the host defense response include NLRC4, PGLYRP1, MMP9, and 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 overexpression in subjects experiencing disease progression, further strengthening the relationship of the transcripts with disease.Integrated analysis of the host transcriptome and microbial signatures demonstrated an apparent host response to the presence of an altered or more abundant microbiome. These responses remained elevated in longitudinal follow-up, suggesting that the bacterial communities of the lower airways may act as persistent stimuli for repetitive alveolar injury in IPF. |
| Databáze: | OpenAIRE |
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