Microbes Are Associated with Host Innate Immune Response in Idiopathic Pulmonary Fibrosis.
Am J Respir Crit Care Med
; 196(2): 208-219, 2017 07 15.
Article
en En
| MEDLINE
| ID: mdl-28157391
ABSTRACT
RATIONALE Differences in the lung microbial community influence idiopathic pulmonary fibrosis (IPF) progression. Whether the lung microbiome influences IPF host defense remains unknown. OBJECTIVES:
To explore the host immune response and microbial interaction in IPF as they relate to progression-free survival (PFS), fibroblast function, and leukocyte phenotypes.METHODS:
Paired microarray gene expression data derived from peripheral blood mononuclear cells as well as 16S ribosomal RNA sequencing data from bronchoalveolar lavage obtained as part of the COMET-IPF (Correlating Outcomes with Biochemical Markers to Estimate Time-Progression in Idiopathic Pulmonary Fibrosis) study were used to conduct association pathway analyses. The responsiveness of paired lung fibroblasts to Toll-like receptor 9 (TLR9) stimulation by CpG-oligodeoxynucleotide (CpG-ODN) was integrated into microbiome-gene expression association analyses for a subset of individuals. The relationship between associated pathways and circulating leukocyte phenotypes was explored by flow cytometry. MEASUREMENTS AND MAINRESULTS:
Down-regulation of immune response pathways, including nucleotide-binding oligomerization domain (NOD)-, Toll-, and RIG1-like receptor pathways, was associated with worse PFS. Ten of the 11 PFS-associated pathways correlated with microbial diversity and individual genus, with species accumulation curve richness as a hub. Higher species accumulation curve richness was significantly associated with inhibition of NODs and TLRs, whereas increased abundance of Streptococcus correlated with increased NOD-like receptor signaling. In a network analysis, expression of up-regulated signaling pathways was strongly associated with decreased abundance of operational taxonomic unit 1341 (OTU1341; Prevotella) among individuals with fibroblasts responsive to CpG-ODN stimulation. The expression of TLR signaling pathways was also linked to CpG-ODN responsive fibroblasts, OTU1341 (Prevotella), and Shannon index of microbial diversity in a network analysis. Lymphocytes expressing C-X-C chemokine receptor 3 CD8 significantly correlated with OTU1348 (Staphylococcus).CONCLUSIONS:
These findings suggest that host-microbiome interactions influence PFS and fibroblast responsiveness.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fibrosis Pulmonar Idiopática
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Microbiota
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Inmunidad Innata
Tipo de estudio:
Risk_factors_studies
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2017
Tipo del documento:
Article