Cytoplasmic DNA triggers the activation of the innate immune system. While downstream signaling components have been characterized, the DNA sensing components remain largely elusive. We performed a systematic proteomics screen for proteins that associate with DNA, traversed to a screen for IFN--induced transcripts. We identified DSIRE (DNA sensor for the IL-1 response, previously called AIM2) as a candidate cytoplasmic sensor. DSIRE showed a marked selectivity for double-stranded DNA. DSIRE can recruit the inflammasome adaptor ASC and gets redistributed to ASC speckles upon coexpression of ASC. RNAi-mediated reduction of DSIRE expression led to an impairment in IL-1 maturation. Reconstitution of unresponsive cells with DSIRE, ASC, caspase 1 and IL-1 showed that DSIRE is sufficient for inflammasome activation. Overall, our data strongly suggest that DSIRE is a cytoplasmic DNA sensor for the inflammasome.
An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome.
No sample metadata fields
View SamplesHuh7/5-2 cells (Binder et al., Hepatology 2007) were mock infected (DMEM) (time points 4 and 48 h) or infected with the chimeric HCV virus Jc1 (Pietschmann et al., PNAS 2006) (all time points).
Viral immune modulators perturb the human molecular network by common and unique strategies.
Specimen part, Time
View SamplesBackground
Distinct roles of the Gcn5 histone acetyltransferase revealed during transient stress-induced reprogramming of the genome.
Treatment
View SamplesThe data provide information expression profile in yeast for 5 different physioloigcal conditions during stress adpatation and stress recovery (normal growth, during stress adaptation, after stress adaptation, under stress recovery, after stress recovery) in yeast. The purpose of the study is to understand how histone acetyltransferase HATs (Gcn5) apply it is function in gene regulation by changing global or local histone acetylation level under different physiological conditions.
Distinct roles of the Gcn5 histone acetyltransferase revealed during transient stress-induced reprogramming of the genome.
Treatment
View SamplesIn the marrow and lymphatic tissues, chronic lymphocytic leukemia (CLL) cells interact with accessory cells that constitute the leukemia microenvironment. In lymphatic tissues, CLL cells are interspersed with CD68+ nurselike cells (NLC) and T cells. However, the mechanism regulating co-localization of CLL cells and these accessory cells are largely unknown. To dissect the molecular cross-talk between CLL and NLC, we profiled the gene expression of CD19-purified CLL cells before and after co-culture with NLC. NLC co-culture induced high-level expression of B cell maturation antigen (BCMA) and two chemoattractants (CCL3, CCL4) by CLL cells. Supernatants from CLL-NLC co-cultures revealed high CCL3/CCL4 protein levels. B cell receptor triggering also induced a robust induction of CCL3 and CCL4 expression by CLL cells, which was almost completely abrogated by a specific Syc inhibitor, R406. High CCL3 and CCL4 plasma levels in CLL patients suggest that activation of this pathway plays a role in vivo. These studies reveal a novel mechanism of cross-talk between CLL cells and their microenvironment, namely the secretion of two T cell chemokines by CLL-NLC interaction and in response to BCR stimulation. Through these chemokines, CLL cells can recruit accessory cells, and thereby actively create a microenvironment that favors their growth and survival.
High-level expression of the T-cell chemokines CCL3 and CCL4 by chronic lymphocytic leukemia B cells in nurselike cell cocultures and after BCR stimulation.
No sample metadata fields
View SamplesWe used microarrays to detect the differences in gene-expression of the periontal ligament between patients with healthy periodontal ligament and patients with periodontitis
The pathology of bone tissue during peri-implantitis.
Specimen part
View SamplesIn this study we want to ascertain the differences and similarities of infected and inflammated peri implant tissue versus healthy peri implant tissue at the mRNA level.
The pathology of bone tissue during peri-implantitis.
Specimen part, Disease, Disease stage
View SamplesTo investigate the importance of STAT3 in the establishment of ES cells we have in a first step derived stable pluripotent embryonic stem cells from transgenic FVB mice expressing a conditional tamoxifen dependent STAT3-MER fusion protein. In a second step, STAT3-MER overexpressing cells were used to identify STAT3 pathway-related genes by expression profiling in order to identify new key-players involved in maintenance of pluripotency in ES cells.
Expression profiling in transgenic FVB/N embryonic stem cells overexpressing STAT3.
No sample metadata fields
View SamplesEfficient processing of target antigens by the ubiquitin-proteasome-system (UPS) is essential for treatment of cancers by T cell therapies. However, immune escape due to impaired expression of IFN--inducible components of the antigen presentation machinery and consequent inefficient processing of HLA-dependent tumor epitopes can be one important reason for failure of such therapies. Here, we show that repeated short-term co-cultures of Melan-A/MART-1 tumor antigen-expressing melanoma cells with Melan-A/MART-1 (26-35)-specific CTL led to the generation of clones resistant to CTL-mediated cell death. To determine which of the UPS components and its associated pathways was responsible for CTL escape; three UKRV-Mel-15a clones were subjected to microarray gene expression analysis.
Exposure to Melan-A/MART-126-35 tumor epitope specific CD8(+)T cells reveals immune escape by affecting the ubiquitin-proteasome system (UPS).
Specimen part
View SamplesWe tested the effects of co-infection on vaccine response to YFV-17D.
Sequential Infection with Common Pathogens Promotes Human-like Immune Gene Expression and Altered Vaccine Response.
Specimen part
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