The enzymes of the poly-ADP-ribose polymerase (PARP) super-family control many relevant cellular processes, but a precise understanding of their activities in different physiological or disease contexts is largely incomplete. We found that transcription of several PARP genes was dynamically regulated upon macrophage activation by several inflammatory stimuli. Specifically, PARP14 was strongly induced by endotoxin stimulation and translocated to the nucleus in stimulated cells. Quantitative mass spectrometry analysis showed that PARP14 bound to a group of interferon-stimulated gene (ISG)-encoded proteins, most with an unknown function, and it was required for their nuclear accumulation. Moreover, PARP14 depletion attenuated transcription of primary antiviral response genes regulated by the transcription factor IRF3, including Ifnb1, thus reducing IFNß production and activation of ISGs involved in the secondary antiviral response. Overall, these data hint at a role of PARP14 in the control of antimicrobial responses and specifically in nuclear activities of a subgroup of ISG-encoded proteins. Overall design: mRNA sequencing of differentially expressed genes in PARP14 WT and KO RAW 264.7 cells, upon: no treatment, LPS, Jak inhibitor or LPS plus Jak inhibitor treatment.
PARP14 Controls the Nuclear Accumulation of a Subset of Type I IFN-Inducible Proteins.
Specimen part, Cell line, Treatment, Subject
View SamplesB220+GL7+ (GC) and B220+GL7- (non-GC) B cells were sorted from SRBC-immunized mice deficient for Hdac3 and wild type controls. RNA-sequencing revealed an upregulation of critical regulators of B cell differentiation in Hdac3-deleted animals. Overall design: 10 days post-immunization with SRBCs, GC and non-GC B cells were sorted and RNA isolated by Trizol extraction for RNA-sequencing. 2 replicates were sequenced for each condition.
Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system.
Specimen part, Cell line, Subject
View SamplesThe enzymes of the poly-ADP-ribose polymerase (PARP) super-family control many relevant cellular processes, but a precise understanding of their activities in different physiological or disease contexts is largely incomplete. We found that transcription of several PARP genes was dynamically regulated upon macrophage activation by several inflammatory stimuli. Specifically, PARP14 was strongly induced by endotoxin stimulation and translocated to the nucleus in stimulated cells. Quantitative mass spectrometry analysis showed that PARP14 bound to a group of interferon-stimulated gene (ISG)-encoded proteins, most with an unknown function, and it was required for their nuclear accumulation. Moreover, PARP14 depletion attenuated transcription of primary antiviral response genes regulated by the transcription factor IRF3, including Ifnb1, thus reducing IFNß production and activation of ISGs involved in the secondary antiviral response. Overall, these data hint at a role of PARP14 in the control of antimicrobial responses and specifically in nuclear activities of a subgroup of ISG-encoded proteins. Overall design: mRNA sequencing of differentially expressed genes in PARP14 WT RAW 264.7 cells, with or without LPS treatment
PARP14 Controls the Nuclear Accumulation of a Subset of Type I IFN-Inducible Proteins.
Specimen part, Cell line, Treatment, Subject
View SamplesmiRNA regulate gene expression at the post-transcriptionnal level. To gain further insight into this process, we analysed by Affymetrix microarray, the transcriptome of Dicer WT or Dicer deleted mouse CD4 T cells.
microRNA-mediated regulation of mTOR complex components facilitates discrimination between activation and anergy in CD4 T cells.
Specimen part
View SamplesInfection of the human host by Streptococcus pneumoniae begins with colonization of the nasopharynx, which is mediated by adherence of bacteria to respiratory epithelium. Several studies have indicated an important role for the pneumococcal capsule in this process. Here, we used microarrays to characterize the in vitro transcriptional response of human nasopharyngeal epithelial Detroit 562 cells to adherence of serotype 2-encapsulated strain D39, serotype 19F-encapsulated strain G54, serotype 4-encapsulated strain TIGR4, and their nonencapsulated derivatives (cps). In total, 322 genes were found to be upregulated in response to adherent pneumococci. Twenty-two genes were commonly induced, including those encoding several cytokines (e.g., IL-1, IL-6), chemokines (e.g., IL-8, CXCL1/2), and transcriptional regulators (e.g., FOS), consistent with an innate immune response mediated by Toll-like receptor signaling. Interestingly, 85% of genes was induced specifically by one or more encapsulated strains, suggestive of a capsule-dependent response. Importantly, purified capsular polysaccharides alone had no effect. Over a third of these loci encoded products predicted to be involved in transcriptional regulation and signal transduction, in particular MAPK signaling pathways. Real-time PCR of a subset of ten genes confirmed microarray data and showed a time-dependent upregulation of especially innate immunity genes. Downregulation of epithelial genes was most pronounced upon adherent D39cps, as 68% of the 161 genes identified was only repressed using this nonencapsulated strain. In conclusion, we identified a subset of host genes specifically induced by encapsulated strains during in vitro adherence, and have demonstrated the complexity of interactions occurring during the initial stages of pneumococcal infection.
Analysis of the in vitro transcriptional response of human pharyngeal epithelial cells to adherent Streptococcus pneumoniae: evidence for a distinct response to encapsulated strains.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Strain-dependent host transcriptional responses to Toxoplasma infection are largely conserved in mammalian and avian hosts.
Cell line, Time
View SamplesToxoplasma gondii is a ubiquitous protozoan pathogen able to infect both mammalian and avian hosts. Surprisingly, just three strains appear to account for the majority of isolates from Europe and N. America.
Strain-dependent host transcriptional responses to Toxoplasma infection are largely conserved in mammalian and avian hosts.
Cell line, Time
View SamplesToxoplasma gondii is a ubiquitous protozoan pathogen able to infect both mammalian and avian hosts. Surprisingly, just three strains appear to account for the majority of isolates from Europe and N. America.
Strain-dependent host transcriptional responses to Toxoplasma infection are largely conserved in mammalian and avian hosts.
Cell line, Time
View SamplesInfection of RAW264.7 cells with RHku80 parasites or mock-infection for 24 hours
Infection by Toxoplasma gondii specifically induces host c-Myc and the genes this pivotal transcription factor regulates.
Cell line
View SamplesToxoplasma gondii is a ubiquitous protozoan pathogen able to infect both mammalian and avian hosts. Surprisingly, just three strains appear to account for the majority of isolates from Europe and N. America.
Strain-dependent host transcriptional responses to Toxoplasma infection are largely conserved in mammalian and avian hosts.
Cell line, Time
View Samples