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GSE41089
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
An efficient innate immune recognition of the intracellular parasite T. cruzi is crucial for host protection against development of Chagas disease, which often leads to multiple organ damage, particularly the heart leading to cardiomyopathy. Mechanisms modulated by MyD88 have been shown to be necessary for resistance against T, cruzi infection. Recently, Nod-like receptors have been shown to play an important role as innate immune sensors, particularly as they relate to inflammasome function, caspase activation, and inflammatory cytokine production. In this study, we aimed to investigate the participation of innate immune responses in general, and inflammasomes in particular, in heart inflammation and cardiac damage upon infection with the T. cruzi parasite.
Publication Title
Apoptosis-associated speck-like protein containing a caspase recruitment domain inflammasomes mediate IL-1β response and host resistance to Trypanosoma cruzi infection.
Sample Metadata Fields
Specimen part
View Samples- Macaca mulatta
- 59 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
CD8+ T-cells inhibit virus replication in SIV-infected rhesus macaques (RM). However, it is unclear to what extent the viral suppression mediated by CD8+ T-cells reflects direct killing of infected cells as opposed to indirect, non-cytolytic mechanisms. In this study, we used functional genomics to investigate potential mechanisms of in vivo viral suppression mediated by CD8+ lymphocytes. Eight chronically SIVmac239-infected RMs underwent CD8+ lymphocyte depletion, and RNA from whole blood was obtained prior to depletion, at the nadir of CD8+ lymphocytes (5 days post-depletion), and during the repopulation phase (11 days post-depletion). Principal components analysis demonstrated that overall gene expression during the nadir of CD8+ T-cells was highly divergent from other intervals. Conversely, the genomic signature of samples from the CD8+ cell rebound phase was similar to that of pre-depletion samples. During CD8+ lymphocyte depletion we detected a strongly significant decrease in the expression of the genes encoding CD8 and CD8 chains, consistent with the near complete CD8+ T-cell depletion measured by flow cytometry. Of note, we observed significant down-regulation of the expression of genes encoding for factors that can suppress SIV replication, including the CCR5-binding chemokine CCL5/Rantes, several retroviral restriction factors (TRIM10, TRIM15, APOBEC3G/H) and defensins. Reduced expression of various genes related to T cell activation and proliferation was also observed. Collectively, these data indicate that depletion of CD8+ lymphocytes in SIV-infected RMs is associated with the establishment of a pattern of gene expression that may result in increased intrinsic permissivity to virus replication.
Publication Title
Transcriptional profiling of experimental CD8(+) lymphocyte depletion in rhesus macaques infected with simian immunodeficiency virus SIVmac239.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 26 Downloadable Samples
Illumina HiSeq 2500
Description
The transcriptomes of FACS-sorted siglec-F+ alveolar macrophages and siglec-f- CD11b+ exudative macrophages from inducible airway GM-CSF over-expressing transgenic mice (DTGM) were compared to non-inducible littermate controls during influenza A virus infection. Overall design: Examination of effect of GM-CSF on airway macrophages during influenza A virus infection
Publication Title
GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Macaca mulatta
- 10 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
Hyperimmune activation is one of the strong predictors of disease progression during pathogenic immunodeficiency virus infections and is mediated in part by sustained type I interferon (IFN) signaling. Combination antiretroviral therapy suppresses hyperimmune activation only partially in HIV-infected individuals. Here, we show that blockade of Programmed Death-1 (PD-1) during chonic SIV infection significantly reduces the expression of transcripts associated with type I IFN signaling in the blood and colorectal tissue of rhesus macaques (RM). The effect of PD-1 blockade on type I IFN signaling was durable and persisted under high viremia, a condition that is seen in nonprogressive SIV infection in their natural hosts. The reduced type I IFN signaling was associated with enhanced expression of some of the junction-associated genes in the colorectal tissue and a profound decrease in LPS levels in plasma suggesting a possible repair of gut associated junctions and decreased microbial translocation. The reduced type I IFN signaling was also associated with enhanced immunity against gut resident pathogenic bacteria, control of gut associated opportunistic infections and survival of SIV-infected RMs. These results reveal novel mechanisms by which PD-1 blockade enhances survival of SIV-infected RMs and have implications for development of novel therapeutic approaches to control HIV/AIDS.
Publication Title
PD-1 blockade during chronic SIV infection reduces hyperimmune activation and microbial translocation in rhesus macaques.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
A cell line was derived from a mammary carcinoma in the transgenic FVB/N-Tg(MMTV-ErbB2)NDL2-5Mul mouse. The line, referred to as “NDL(UCD)” is adapted to standard cell culture and can be transplanted into syngeneic FVB/N mice. The line maintains a stable phenotype over multiple in vitro passages and rounds of in vivo transplantation. The cell line exhibits high expression of ErbB2 and ErbB3 and signaling molecules downstream from ErbB2. The line was previously shown to be reactive to anti-immune checkpoint therapy with responses conducive to immunotherapy studies. Here, using both histology/immunophenotyping and gene expression/microarray analysis, we show that the syngeneic transplant tumors elicit an immune reaction in the adjacent stroma, with additional tumor infiltrating lymphocytes. We also show that this immune activating effect is greater in the syngeneic transplants than in the primary tumors arising in the native transgenic mouse. We further analyzed the PD-1 and PD-L-1 expression in the model and found PD-L1 expression in the tumors and in vitro. In conclusion these data document the validity and utility of this cell line for in vivo preclinical immunotherapy trials. Overall design: Flash frozen NDL(UCD) cell line tumor transplants were sampled and whole-transcriptome analysis was performed by next-generation sequencing (NGS)-based RNA-Sequencing. This series includes three biological replicates of the same cell line grown in three different (but same strain) mouse.
Publication Title
A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
RNAseq analysis of BAFF in vitro-stimulated (6 hours) murine nfkb2fl/flCD19-Cre (furtheron designated as REL) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor NF-kB2 in BAFF-stimulated B cells. Overall design: Splenic B cells from 12-week old relfl/flCD19-Cre and CD19-Cre littermate mice were isolated by magnetic cell separation from splenic mononuclear cells and stimulated in vitro for 6 hours with BAFF. RNA was isolated and submitted for RNA-sequencing on an Illumina HiSeq2000 instrument for 30 million single-ended reads.
Publication Title
Impairment of Mature B Cell Maintenance upon Combined Deletion of the Alternative NF-κB Transcription Factors RELB and NF-κB2 in B Cells.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
RNAseq analysis of CD40 in vitro-stimulated (6 hours) murine nfkb2fl/flCD19-Cre (furtheron designated as REL) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor NF-kB2 in activated B cells. Overall design: Splenic B cells from 12-week old relfl/flCD19-Cre and CD19-Cre littermate mice were isolated by magnetic cell separation from splenic mononuclear cells and stimulated in vitro for 6 hours with anti-CD40 and anti-IgM. RNA was isolated and submitted for RNA-sequencing on an Illumina HiSeq2000 instrument for 30 million single-ended reads.
Publication Title
Impairment of Mature B Cell Maintenance upon Combined Deletion of the Alternative NF-κB Transcription Factors RELB and NF-κB2 in B Cells.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 191 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Genome-wide association studies (GWAS) have been pivotal to increasing our understanding of intestinal disease. However, the mode by which genetic variation results in phenotypic change remains largely unknown, with many associated polymorphisms likely to modulate gene expression. Analyses of expression quantitative trait loci (eQTL) to date indicate that as many as 50% of these are tissue specific. Here we report a comprehensive eQTL scan of intestinal tissue.
Publication Title
Expression quantitative trait loci analysis identifies associations between genotype and gene expression in human intestine.
Sample Metadata Fields
Sex, Disease
View Samples- Macaca mulatta, Cercocebus atys
- 8 Downloadable Samples
- Affymetrix Rhesus Macaque Genome Array (rhesus)
Description
In SIV/HIV infection, the gastrointestinal tissue dominates as an important site due to the impact of massive mucosal CD4 depletion and immune activation-induced tissue pathology. Unlike AIDS-susceptible rhesus macaques, natural hosts do not progress to AIDS and resolve immune activation earlier. Here, we examine the role of dendritic cells in mediating immune activation and disease progression. We demonstrate that plasmacytoid dendritic cells (pDC) in the blood upregulate 7-integrin and are rapidly recruited to the colorectum following a pathogenic SIV infection in rhesus macaques. These pDC were capable of producing proinflammatory cytokines and primed a Tc1 response in vitro. Consistent with the upregulation of 7-integrin on pDC, in vivo blockade of 47-integrin dampened pDC recruitment to the colorectum and resulted in reduced immune activation. The upregulation of 7-integrin expression on pDC in the blood was also observed in HIV-infected humans but not in chronically SIV-infected sooty mangabeys that show low levels of immune activation. Our results uncover a new mechanism by which pDC influence immune activation in colorectal tissue following pathogenic immunodeficiency virus infections.
Publication Title
Plasmacytoid dendritic cells are recruited to the colorectum and contribute to immune activation during pathogenic SIV infection in rhesus macaques.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA-seq analysis of murine eGFP+ relbfl/flnfkb2fl/flCg1-Cre and Cg1-Cre splenic germinal center B cells identifies genes regulated by the transcription factors RELB and p52 (NF-kB2) in germinal center B cells. Overall design: Germinal center B cells from 12-week old relbfl/flnfkb2fl/flCg1-Cre and Cg1-Cre littermate mice immunized with sheep red blood cells (SRBC) were isolated at day 7 after immunization by flow cytometric sorting from splenic mononuclear cells. RNA was isolated, amplified and submitted for RNA-sequencing on an Illumina HiSeq2500 instrument for 35-40 million 2x50 paired-ended reads.
Publication Title
Transcription factors of the alternative NF-κB pathway are required for germinal center B-cell development.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples