Carbon-based nanomaterials including carbon nanotubes (CNTs) have been shown to trigger inflammation. However, how these materials are 'sensed' by immune cells is not known. Here we compared the effects of two carbon-based nanomaterials, single-walled CNTs (SWCNTs) and graphene oxide (GO), on primary human monocyte-derived macrophages. Genome-wide transcriptomics assessment was performed at sub-cytotoxic doses. Pathway analysis of the microarray data revealed pronounced effects on chemokine-encoding genes in macrophages exposed to SWCNTs, but not in response to GO, and these results were validated by multiplex array-based cytokine and chemokine profiling. Conditioned medium from SWCNT-exposed cells acted as a chemoattractant for dendritic cells. Chemokine secretion was reduced upon inhibition of NF-κB, as predicted by upstream regulator analysis of the transcriptomics data, and Toll-like receptors (TLRs) and their adaptor molecule, MyD88 were shown to be important for CCL5 secretion. Moreover, a specific role for TLR2/4 was confirmed by using reporter cell lines. Computational studies to elucidate how SWCNTs may interact with TLR4 in the absence of a protein corona suggested that binding is guided mainly by hydrophobic interactions. Taken together, these results imply that CNTs may be 'sensed' as pathogens by immune cells.

• MeSH
• chemokiny metabolismus   MeSH
• cytotoxicita imunologická MeSH
• genové regulační sítě MeSH
• hydrofobní a hydrofilní interakce MeSH
• interakce hostitele a patogenu imunologie   MeSH
• kultivované buňky MeSH
• lidé MeSH
• makrofágy fyziologie   ultrastruktura   MeSH
• molekulární konformace MeSH
• molekulární modely MeSH
• nanotrubičky uhlíkové * chemie   MeSH
• reprodukovatelnost výsledků MeSH
• signální transdukce MeSH
• stanovení celkové genové exprese MeSH
• toll-like receptory chemie   metabolismus   MeSH
• transkriptom MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: We set out to explore associations between the stool bacteriome profiles and early-onset islet autoimmunity, taking into account the interactions with the virus component of the microbiome. METHODS: Serial stool samples were longitudinally collected from 18 infants and toddlers with early-onset islet autoimmunity (median age 17.4 months) followed by type 1 diabetes, and 18 tightly matched controls from the Finnish Diabetes Prediction and Prevention (DIPP) cohort. Three stool samples were analyzed, taken 3, 6, and 9 months before the first detection of serum autoantibodies in the case child. The risk of islet autoimmunity was evaluated in relation to the composition of the bacteriome 16S rDNA profiles assessed by mass sequencing, and to the composition of DNA and RNA viromes. RESULTS: Four operational taxonomic units were significantly less abundant in children who later on developed islet autoimmunity as compared to controls-most markedly the species of Bacteroides vulgatus and Bifidobacterium bifidum. The alpha or beta diversity, or the taxonomic levels of bacterial phyla, classes or genera, showed no differences between cases and controls. A correlation analysis suggested a possible relation between CrAssphage signals and quantities of Bacteroides dorei. No apparent associations were seen between development of islet autoimmunity and sequences of yet unknown origin. CONCLUSIONS: The results confirm previous findings that an imbalance within the prevalent Bacteroides genus is associated with islet autoimmunity. The detected quantitative relation of the novel "orphan" bacteriophage CrAssphage with a prevalent species of the Bacteroides genus may exemplify possible modifiers of the bacteriome.

• MeSH
• autoimunita * MeSH
• autoimunitní nemoci krev   epidemiologie   etiologie   imunologie   MeSH
• Bacteroides klasifikace   imunologie   izolace a purifikace   virologie   MeSH
• bakteriální RNA chemie   metabolismus   MeSH
• bakteriofágy klasifikace   imunologie   izolace a purifikace   MeSH
• diabetes mellitus 1. typu krev   epidemiologie   etiologie   imunologie   MeSH
• dítě MeSH
• dysbióza imunologie   mikrobiologie   patofyziologie   virologie   MeSH
• feces mikrobiologie   virologie   MeSH
• fylogeneze MeSH
• kohortové studie MeSH
• Langerhansovy ostrůvky imunologie   MeSH
• lidé MeSH
• longitudinální studie MeSH
• molekulární typizace MeSH
• nemocnice univerzitní MeSH
• prospektivní studie MeSH
• riziko MeSH
• RNA ribozomální 16S chemie   metabolismus   MeSH
• RNA virová chemie   metabolismus   MeSH
• střevní mikroflóra imunologie   MeSH
• studie případů a kontrol MeSH
• výpočetní biologie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Finsko epidemiologie   MeSH

BACKGROUND: Next generation sequencing (NGS) technology allows laboratories to investigate virome composition in clinical and environmental samples in a culture-independent way. There is a need for bioinformatic tools capable of parallel processing of virome sequencing data by exactly identical methods: this is especially important in studies of multifactorial diseases, or in parallel comparison of laboratory protocols. RESULTS: We have developed a web-based application allowing direct upload of sequences from multiple virome samples using custom parameters. The samples are then processed in parallel using an identical protocol, and can be easily reanalyzed. The pipeline performs de-novo assembly, taxonomic classification of viruses as well as sample analyses based on user-defined grouping categories. Tables of virus abundance are produced from cross-validation by remapping the sequencing reads to a union of all observed reference viruses. In addition, read sets and reports are created after processing unmapped reads against known human and bacterial ribosome references. Secured interactive results are dynamically plotted with population and diversity charts, clustered heatmaps and a sortable and searchable abundance table. CONCLUSIONS: The Vipie web application is a unique tool for multi-sample metagenomic analysis of viral data, producing searchable hits tables, interactive population maps, alpha diversity measures and clustered heatmaps that are grouped in applicable custom sample categories. Known references such as human genome and bacterial ribosomal genes are optionally removed from unmapped ('dark matter') reads. Secured results are accessible and shareable on modern browsers. Vipie is a freely available web-based tool whose code is open source.

• MeSH
• genetická variace MeSH
• genomika metody   MeSH
• internet * MeSH
• lidé MeSH
• mikrobiota genetika   MeSH
• software * MeSH
• viry genetika   MeSH
• vysoce účinné nukleotidové sekvenování * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH