RNA-seq analysis of PBMCs with TLR1-1805TT and TLR1-1805GG genotypes stimulated and restimulated (innate immune tolerance induction) with B. burgdorferi.
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 2500
ORGANISM(S): Homo sapiens
SUBMITTER: Morgan Williams
PROVIDER: E-MTAB-16016 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Background: Lyme borrelia genotypes differ in their capacity to cause disseminated disease. Gene array analysis was employed to profile the host transcriptome induced by Borrelia burgdorferi strains with different capacities for causing disseminated disease in the blood of C3H/HeJ mice during early infection. Results: Borrelia burgdorferi B515, a clinical isolate that causes disseminated infection in mice, differentially regulated 236 transcripts (P<0.05 by ANOVA, with fold change of at least 2). The 216 significantly induced transcripts included IFN-responsive genes and genes involved in immunity and inflammation. In contrast, B. burgdorferi B331, a clinical isolate that causes transient skin infection but does not disseminate in C3H/HeJ mice, stimulated changes in only a few genes (1 induced, 4 repressed). Transcriptional regulation of type I IFN and IFN-related genes was measured by quantitative RT-PCR in mouse skin biopsies collected from the site of infection 24 hours after inoculation with B. burgdorferi. The mean values for transcript of Ifnb, Cxcl10, Gbp1, Ifit1, Ifit3, Irf7, Mx1, and Stat2, were found to be significantly increased in B. burgdorferi strain B515-infected mice relative to the control group. In contrast, transcription of these genes was not significantly changed in response to B. burgdorferi strain B331 or B31-4, a mutant that is unable to disseminate. Conclusions: These results establish a positive association between the disseminating capacity of B. burgdorferi and early type I IFN induction in a murine model of Lyme disease.
2016-03-25 | E-MTAB-3325 | biostudies-arrayexpress
Project description:Borrelia burgdorferi, the agent of Lyme disease, promotes pro-inflammatory changes in endothelium that lead to the recruitment of leukocytes. The host immune response to infection results in increased levels of IFN-gamma in the serum and lesions of Lyme disease patients that correlate with greater severity of disease. Therefore, the effect of IFN-gamma on the gene expression profile of primary human endothelial cells exposed to B. burgdorferi was determined. B. burgdorferi and IFN-gamma synergistically augmented the expression of 34 genes, seven of which encode chemokines. Six of these (CCL7, CCL8, CX3CL1, CXCL9, CXCL10, and CXCL11) attract T lymphocytes, and one (CXCL2) is specific for neutrophils. Synergistic production of the attractants for T cells was confirmed at the protein level. IL-1beta, TNF-alpha, and LPS also cooperated with IFN-gamma to induce synergistic production of CXCL10 by endothelium, indicating that IFN-gamma potentiates inflammation in concert with a variety of mediators. An in vitro model of the blood vessel wall revealed that an increased number of human T lymphocytes traversed endothelium exposed to B. burgdorferi and IFN-gamma, as compared to unstimulated endothelial monolayers. In contrast, addition of IFN-gamma diminished the migration of neutrophils across B. burgdorferi-activated endothelium. IFN-gamma thus alters gene expression by endothelium exposed to B. burgdorferi in a manner that promotes recruitment of T cells and suppresses that of neutrophils. This modulation may facilitate the development of chronic inflammatory lesions in Lyme disease. Experiment Overall Design: Human umbilical vein endothelial cells (HUVEC) were stimulated with Interferon-gamma (IFN-g), Borrelia burgdorferi or both IFN-g and Borrelia or were left unstimulated. Affymetrix HGU133 plus 2.0 slides were used in duplicate for each condition.
2008-06-14 | E-GEOD-6092 | biostudies-arrayexpress
Project description:Lyme disease is a result from an infection by the spirochete Borrelia burgdorferi, and is the leading vector-borne disease in North America. Due to the genomic and proteomic variability of different B. burgdorferi isolates, the study and further comparison of their proteome is key to understand the biology and infectivity of these spirochetes. Mass spectrometry-based proteomics was used to assemble peptide datasets of laboratory isolates B31, MM1, B31-ML23, and the infective isolates B31-5A4, B31-A3, and 297, as well as other public datasets, and is publicly available as the Borrelia PeptideAtlas (http://www.peptideatlas.org/builds/borrelia/). These datasets include information on total proteome, secretome, and membrane proteome of the B. burgdorferi.
2025-05-06 | PXD042072 | Pride
Project description:Lyme disease is a result from an infection by the spirochete Borrelia burgdorferi, and is the leading vector-borne disease in North America. Due to the genomic and proteomic variability of different B. burgdorferi isolates, the study and further comparison of their proteome is key to understand the biology and infectivity of these spirochetes. Mass spectrometry-based proteomics was used to assemble peptide datasets of laboratory isolates B31, MM1, B31-ML23, and the infective isolates B31-5A4, B31-A3, and 297, as well as other public datasets, and is publicly available as the Borrelia PeptideAtlas (http://www.peptideatlas.org/builds/borrelia/). These datasets include information on total proteome, secretome, and membrane proteome of the B. burgdorferi.
2024-09-03 | PXD046281 | Pride
Project description:The similarity of Lyme borreliosis to other diseases and the complex pathogenesis cause diagnostic and therapeutic difficulties. Changes at the cellular and molecular level after Borrelia sp. infection remain still poorly understood. Therefore, the present study focused on the gene expression in human dermal fibroblasts in differentiation of infection with Borrelia garinii, Borrelia afzelii and Borrelia burgdorferi sensu stricto spirochetes. For microarray analysis 10 samples were used: 3 control samples - K, 2 samples of NHDF cells infected with Borrelia garinii - G, 2 samples of NHDF cells infected with Borrelia afzelii - A and 3 samples of NHDF cells infected with Borrelia burgdorferi sensu stricto - SS.
2015-05-12 | E-GEOD-68741 | biostudies-arrayexpress
Project description:Apicomplexan protozoan parasite Babesia microti (Bm) and spirochetal bacterium Borrelia burgdorferi are tick-transmitted pathogens that cause babesiosis and Lyme disease, respectively and increasingly cause co-infections in the endemic regions of the United States. More severe manifestations of Lyme disease are displayed during these co-infections relative to that by B. burgdorferi alone, suggesting differential host responses could play roles during these host-microbes interactions. In C3H mouse model, we confirmed Bm parasitemia by microscopic examination of Giemsa-stained blood smears while live-imaging of mice infected with our bioluminescent B. burgdorferi N40 strain allowed monitoring of disseminated infection levels. Gradation of temporal host genes expression was unveiled by proteomic analyses of blood samples. At 2 weeks post-infection, in naive versus N40+Bm, N40, and Bm infected mice, 31, 96, 76, and 22 unique proteins, respectively were detected while a convergence of 3,359 common proteins were identified across all groups. Notably, the proteomic landscape showed a significant overlap between naive and Bm infected mice and their most pronounced differences observed with the co-infected group. Using Volcano plots, upregulation of proteins associated with cellular and metabolic processes particularly in the N40+Bm co-infected mice were observed. At 4 weeks post-infection, distinct proteomic profile among naive, Bm, and co-infection mice emphasizes stimulation of distinct host responses after peak burden of pathogens. Host proteins overlap diminished significantly during the persistent infection at 16 weeks. Principal component analysis underscores stage-specific protein clustering. These findings illuminate intricate interactions between pathogens and host proteome dynamics that could provide insight into changes occurring throughout infection, especially during co-infection.
2025-07-14 | PXD054200 | Pride
Project description:As adherence and entry of a pathogen into a host cell are two key components to an infection, identifying the molecular mechanisms responsible for cellular association will provide a better understanding of a microbeâs ability for pathogenesis. We previously established an in vitro model for B. burgdorferi invasion of human neuroglial cells. To expand on our earlier study, we performed B. burgdorferi whole-genome expression analysis following a 20-hour infection of human neuroglial cells to identify borrelial genes that were differentially regulated during cellular attachment and invasion as compared with cultured Borrelia in cell-free medium. This study identifies several regulated genes, the products of which may be important mediators for cellular pathogenesis. Keywords: in-vitro H4 neuroglial cells infected with B. burgdorferi A 20-hour incubation was performed, and this time point included B. burgdorferi that were both intra- and extra-cellularly localized to the H4 cells (Livengood and Gilmore, 2006). After B. burgdorferi infection of these cells, the total cellular RNA preparation (including H4 RNA, and Borrelia RNA) was enriched for prokaryotic RNA, which concentrated the bacterial message, but did not completely eliminate the eukaryotic RNA (data not shown). Therefore, as a control in our arrays, eukaryotic RNA from the human H4 cells was also purified and hybridized to the array. To control for Borrelia cell-free gene expression, the data from the experimental conditions (B. burgdorferi infected human cells) was normalized to borrelial expression following growth in BSK and a 20 hour incubation in DMEM tissue culture media. As with the experimental samples, both controls were assayed in triplicate.
2010-05-26 | E-GEOD-8219 | biostudies-arrayexpress
Project description:The bacterial stringent response is triggered by deficiencies of available nutrients andother environmental stresses. It is mediated by 5'-triphosphate-guanosine-3'- diphosphate and 5'-diphosphate-guanosine-3'-diphosphate (collectively (p)ppGpp) and generates global changes in gene expression and metabolism that enable bacteria to adapt to and survive these challenges. Borrelia burgdorferi encounters multiple stressors in its cycling between ticks and mammals that could trigger the stringent response. We have previously shown that the B. burgdorferi stringent response is mediated by a single enzyme, RelBbu, with both (p)ppGpp synthase and hydrolase activities, and that a B. burgdorferi 297 relBbu null deletion mutant was defective in adapting to stationary phase, incapable of down-regulating synthesis of rRNA and could not infect mice. We have now used this deletion mutant and microarray analysis to identify genes comprising the rel regulon in B. burgdorferi cultured at 34°C, and found that transcription of genes involved in glycerol metabolism is induced by relBbu. Culture of the wild-type parental strain, the relBbu deletion mutant and its complemented derivative at 34°C and 25°C in media containing glucose or glycerol as principal carbon sources revealed a growth defect in the mutant, most evident at the lower temperature. Transcriptional analysis of the glp operon for glycerol uptake and metabolism in these three strains confirmed that relBbu was necessary and sufficient to increase transcription of this operon in the presence of glycerol at both temperatures, and particularly at 25°C. These results confirm and extend previous findings regarding the stringent response in B. burgdorferi. They also demonstrate that the stringent response regulates glycerol metabolism in this organism and is likely crucial for its optimal growth in ticks.
2015-01-30 | E-MTAB-3029 | biostudies-arrayexpress
Project description:Borelia burgdorferi, the causative agent of the Lyme disease, cycles between a vector (tick) and the mammalian host. Our principal goal is to study how B. burgdorferi adapts its metabolism to colonize and survive in the tick. We established the first growth-phase related acetylome and demonstrated the role of acetylation on central metabolism regulation. We also demonstrated that acetyl phosphate is the primary acetyl donor in B. burgdorferi.
2018-09-24 | PXD010065 | Pride
Project description:Borrelia burgdorferi, the agent of Lyme disease, promotes pro-inflammatory changes in endothelium that lead to the recruitment of leukocytes. The host immune response to infection results in increased levels of IFN-gamma in the serum and lesions of Lyme disease patients that correlate with greater severity of disease. Therefore, the effect of IFN-gamma on the gene expression profile of primary human endothelial cells exposed to B. burgdorferi was determined. B. burgdorferi and IFN-gamma synergistically augmented the expression of 34 genes, seven of which encode chemokines. Six of these (CCL7, CCL8, CX3CL1, CXCL9, CXCL10, and CXCL11) attract T lymphocytes, and one (CXCL2) is specific for neutrophils. Synergistic production of the attractants for T cells was confirmed at the protein level. IL-1beta, TNF-alpha, and LPS also cooperated with IFN-gamma to induce synergistic production of CXCL10 by endothelium, indicating that IFN-gamma potentiates inflammation in concert with a variety of mediators. An in vitro model of the blood vessel wall revealed that an increased number of human T lymphocytes traversed endothelium exposed to B. burgdorferi and IFN-gamma, as compared to unstimulated endothelial monolayers. In contrast, addition of IFN-gamma diminished the migration of neutrophils across B. burgdorferi-activated endothelium. IFN-gamma thus alters gene expression by endothelium exposed to B. burgdorferi in a manner that promotes recruitment of T cells and suppresses that of neutrophils. This modulation may facilitate the development of chronic inflammatory lesions in Lyme disease. Keywords: Cell response to inflammatory stimuli
2007-01-05 | GSE6092 | GEO