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Microbes associate with host innate immune response in idiopathic pulmonary fibrosis

ABSTRACT: The goal of this study is to explore molecular mechanisms underpinning the progression-associated host-microbial interactions in IPF. Multi-omics analysis revealed that the majority (8/11) of the progression-associated pathways were involved in inflammatory response and pattern recognition receptors (PRRs), including NOD-, TOLL- and RIG-I-like receptor pathways. Microbial community richness was correlated with all of the three PRRs (Pearson's p<0.007). The known IPF-progression marker Streptococcus (OTU1345) was correlated with NOD like receptor signaling pathway (p=0.047). Up-regulated genes in PBMCs of CpG-ODN responsive patients were over-represented in 22 canonical pathways (FDR<0.01). Network modeling revealed that 14/22 pathways were significantly correlated with community diversity (Shannon's index) and three genera (Otu1341 Prevotella, OTU1348 Staphylococcus, and OTU1302 Pseuodomonadacea), as well as 10/11 host gene co-expression modules. Toll-like receptor signaling pathway was mutually linked by CpG-response, Otu1341 and microbial Shannon's index. Notably, OTU1341 and IPF-progression marker OTU1348 were also correlated with TLR9 (r=0.48, p=3x10-5; r=0.38, p=0.002, respectively). These findings suggest that PRR and immune response signaling pathways play a central role in PFS-associated host-microbial interactions and the probifbrotic differentiation induced by CpG-ODN upon TLR9 stimulation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE85268 | GEO | 2016/09/15

SECONDARY ACCESSION(S): PRJNA337976

REPOSITORIES: GEO

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Project description:Toll-like receptors (TLRs) are mediators in the innate immune response by recognizing nucleic acids derived from microbial components as for TLR9 binding ability for CpG rich bacterial DNA. We studied the differential expression by microarrays of all known T-UCRs and near genes in a series of 6 primary B-CLL cases cells comparing cells treated in vitro with CpG ODN versus mock controls.

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