8 research outputs found
A Comparative Transcriptome Analysis of Human and Porcine Choroid Plexus Cells in Response to Streptococcus suis Serotype 2 Infection Points to a Role of Hypoxia
Streptococcus suis (S. suis) is an important opportunistic pathogen, which can cause
septicemia and meningitis in pigs and humans. Previous in vivo observations in S. suisinfected
pigs revealed lesions at the choroid plexus (CP). In vitro experiments with primary
porcine CP epithelial cells (PCPEC) and human CP epithelial papilloma (HIBCPP) cells
demonstrated that S. suis can invade and traverse the CP epithelium, and that the CP
contributes to the inflammatory response via cytokine expression. Here, next generation
sequencing (RNA-seq) was used to compare global transcriptome profiles of PCPEC and
HIBCPP cells challenged with S. suis serotype (ST) 2 infected in vitro, and of pigs infected
in vivo. Identified differentially expressed genes (DEGs) were, amongst others, involved in
inflammatory responses and hypoxia. The RNA-seq data were validated via quantitative
PCR of selected DEGs. Employing Gene Set Enrichment Analysis (GSEA), 18, 28, and 21
enriched hallmark gene sets (GSs) were identified for infected HIBCPP cells, PCPEC, and
in the CP of pigs suffering from S. suis ST2 meningitis, respectively, of which eight GSs
overlapped between the three different sample sets. The majority of these GSs are
involved in cellular signaling and pathways, immune response, and development,
including inflammatory response and hypoxia. In contrast, suppressed GSs observed
during in vitro and in vivo S. suis ST2 infections included those, which were involved in
cellular proliferation and metabolic processes. This study suggests that similar cellular
processes occur in infected human and porcine CP epithelial cells, especially in terms of
inflammatory response
Shorter telomeres correlate with an increase in the number of uniparental disomies in patients with chronic lymphocytic leukemia.
This study investigated the correlation of the extent of chromosomal aberrations including uniparental disomies (UPDs) by SNP-chip analysis and FISH to telomere length in 46 patients with CLL. CLL harboring high risk aberrations, i.e. deletions of 11q22-23 or 17p13, had significantly shorter telomeres (higher ΔTL) compared to patients with CLL without such abnormalities. Patients with high chromosomal aberration rates had a worse overall survival compared to cases with lower aberration rates. Interestingly, however, an increase was found in the number of UPDs with shorter telomeres. These findings support the idea that telomeres in CLL cells play a role in the overall chromosome stability and could be involved in the occurrence of UPDs
A Comparative Transcriptome Analysis of Human and Porcine Choroid Plexus Cells in Response to Streptococcus suis Serotype 2 Infection Points to a Role of Hypoxia
Streptococcus suis (S. suis) is an important opportunistic pathogen, which can cause
septicemia and meningitis in pigs and humans. Previous in vivo observations in S. suisinfected
pigs revealed lesions at the choroid plexus (CP). In vitro experiments with primary
porcine CP epithelial cells (PCPEC) and human CP epithelial papilloma (HIBCPP) cells
demonstrated that S. suis can invade and traverse the CP epithelium, and that the CP
contributes to the inflammatory response via cytokine expression. Here, next generation
sequencing (RNA-seq) was used to compare global transcriptome profiles of PCPEC and
HIBCPP cells challenged with S. suis serotype (ST) 2 infected in vitro, and of pigs infected
in vivo. Identified differentially expressed genes (DEGs) were, amongst others, involved in
inflammatory responses and hypoxia. The RNA-seq data were validated via quantitative
PCR of selected DEGs. Employing Gene Set Enrichment Analysis (GSEA), 18, 28, and 21
enriched hallmark gene sets (GSs) were identified for infected HIBCPP cells, PCPEC, and
in the CP of pigs suffering from S. suis ST2 meningitis, respectively, of which eight GSs
overlapped between the three different sample sets. The majority of these GSs are
involved in cellular signaling and pathways, immune response, and development,
including inflammatory response and hypoxia. In contrast, suppressed GSs observed
during in vitro and in vivo S. suis ST2 infections included those, which were involved in
cellular proliferation and metabolic processes. This study suggests that similar cellular
processes occur in infected human and porcine CP epithelial cells, especially in terms of
inflammatory response
Concepts in mature T-cell lymphomas - highlights from an international joint symposium on T-cell immunology and oncology
Growing attention in mature T-cell lymphomas/leukemias (MTCL) is committed to more accurate and meaningful classifications, improved pathogenetic concepts and expanded therapeutic options. This requires considerations of the immunologic concepts of T-cell homeostasis and the specifics of T-cell receptor (TCR) affinities and signaling. Scientists from various disciplines established the CONTROL-T research unit and in an international conference on MTCL they brought together experts from T-cell immunity, oncology, immunotherapy and systems biology. We report here meeting highlights on the covered topics of diagnostic pitfalls, implications by the new WHO classification, insights from discovered genomic lesions as well as TCR-centric concepts of cellular dynamics in host defense, auto-immunity and tumorigenic clonal escape, including predictions to be derived from in vivo imaging and mathematical modeling. Presentations on novel treatment approaches were supplemented by strategies of optimizing T-cell immunotherapies. Work packages, that in joint efforts would advance the field of MTCL more efficiently, are identified
A Comparative Transcriptome Analysis of Human and Porcine Choroid Plexus Cells in Response to Streptococcus suis Serotype 2 Infection Points to a Role of Hypoxia
Streptococcus suis (S. suis) is an important opportunistic pathogen, which can cause
septicemia and meningitis in pigs and humans. Previous in vivo observations in S. suisinfected
pigs revealed lesions at the choroid plexus (CP). In vitro experiments with primary
porcine CP epithelial cells (PCPEC) and human CP epithelial papilloma (HIBCPP) cells
demonstrated that S. suis can invade and traverse the CP epithelium, and that the CP
contributes to the inflammatory response via cytokine expression. Here, next generation
sequencing (RNA-seq) was used to compare global transcriptome profiles of PCPEC and
HIBCPP cells challenged with S. suis serotype (ST) 2 infected in vitro, and of pigs infected
in vivo. Identified differentially expressed genes (DEGs) were, amongst others, involved in
inflammatory responses and hypoxia. The RNA-seq data were validated via quantitative
PCR of selected DEGs. Employing Gene Set Enrichment Analysis (GSEA), 18, 28, and 21
enriched hallmark gene sets (GSs) were identified for infected HIBCPP cells, PCPEC, and
in the CP of pigs suffering from S. suis ST2 meningitis, respectively, of which eight GSs
overlapped between the three different sample sets. The majority of these GSs are
involved in cellular signaling and pathways, immune response, and development,
including inflammatory response and hypoxia. In contrast, suppressed GSs observed
during in vitro and in vivo S. suis ST2 infections included those, which were involved in
cellular proliferation and metabolic processes. This study suggests that similar cellular
processes occur in infected human and porcine CP epithelial cells, especially in terms of
inflammatory response
A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma
The genetic hallmark of Burkitt lymphoma (BL) is the t(8;14)(q24;q32) and its variants leading to activation of the MYC oncogene. It is a matter of debate whether true BL without MYC translocation exists. Here, we identified 59 lymphomas concordantly called BL by 2 gene expression classifiers among 753 B-cell lymphomas. Only 2 (3%) of these 59 molecular BL lacked a MYC translocation, which both shared a peculiar pattern of chromosome 11q aberration characterized by interstitial gains including 11q23.2-q23.3 and telomeric losses of 11q24.1-qter. We extended our analysis to 17 MYC-negative high-grade B-cell lymphomas with a similar 11q aberration and showed this aberration to be recurrently associated with morphologic and clinical features of BL. The minimal region of gain was defined by high-level amplifications in 11q23.3 and associated with overexpression of genes including PAFAH1B2 on a transcriptional and protein level. The recurrent region of loss contained a focal homozygous deletion in 11q24.2-q24.3 including the ETS1 gene, which was shown to be mutated in 4 of 16 investigated cases. These findings indicate the existence of a molecularly distinct subset of B-cell lymphomas reminiscent of BL, which is characterized by deregulation of genes in 11q