Time course RNA-Seq analysis of wildtype and Nlrx1 deficient bone marrow derived monocytoid dendritic cells indicate decision tree in response to A. fumigatus viable conidia
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ABSTRACT:
PROVIDER: PRJNA602342 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10917521.fastq.gz | Fastqsanger.gz | |||
| SRR10917522.fastq.gz | Fastqsanger.gz | |||
| SRR10917523.fastq.gz | Fastqsanger.gz | |||
| SRR10917524.fastq.gz | Fastqsanger.gz | |||
| SRR10917525.fastq.gz | Fastqsanger.gz |
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Project description:RNA-Seq analysis of gene expression changes by wildtype and Nlrx1 deficient BEAS-2B airway epithelial cells in response to A. fumigatus viable conidia
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Project description:Chronic innate immune activation in the central nervous system (CNS) significantly contributes to neurodegeneration in progressive multiple sclerosis (MS). Using multiple EAE models, we explored the potential of the innate immune sensor NLRX1 to protect neurons in the anterior visual pathway from inflammatory neurodegeneration. To do this, we assessed retinal ganglion cell (RGC) density and optic nerve axonal degeneration, gliosis, and T-cell infiltration in Nlrx1-/- and wild-type (WT) EAE mice. Our results indicate that Nlrx1-/- mice exhibit significantly increased RGC loss and axonal injury compared to WT mice in both active immunization EAE and spontaneous opticospinal encephalomyelitis models. Adoptive transfer experiments, in which wild type T cells were transferred into lymphocyte-deficient Rag-/- mice to minimize the effects of Nlrx1 knockout on peripheral lymphocyte priming, revealed more severe microgliosis and astrogliosis in the optic nerve of Nlrx1-/-Rag-/- mice compared to Rag-/- mice, suggesting a regulatory role of NLRX1 in innate immune compartments. Transcriptome analysis in primary astrocytes demonstrated that NLRX1 negatively regulates TLR-mediated NF-κB activation. The novel pharmacologic NLRX1 activator LABP-66 decreased LPS-mediated gene expression of inflammatory cytokines and chemokines in mixed glial cultures. Moreover, treating EAE mice with oral LABP-66 after the onset of paralysis resulted in less anterior visual pathway neurodegeneration compared to vehicle. These data suggest that a pharmacologic NLRX1 activators attenuates glial immune activation and has the potential to limit inflammatory neurodegeneration in diseases, such as MS, where chronic CNS-compartmentalized inflammation may drive neurodegenerative pathology. This study highlights that NLRX1 could serve as a promising target for neuroprotection in progressive MS and other neurodegenerative diseases where chronic compartmentalized innate immune activation and neuroinflammation play a role.
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Project description:Genome-wide analysis was performed to assess the transcriptional landscape of germinating A. niger conidia using GeneChips. The metabolism of storage compounds during conidial germination was also examined and compared to the transcript levels from associated genes. The transcriptome of dormant conidia was shown to be highly differentiated from that of germinating conidia and major changes in response to environmental shift occurred within the first hour of germination. The breaking of dormancy was associated with increased transcript levels of genes involved in the biosynthesis of proteins, RNA turnover and respiratory metabolism. Increased transcript levels of genes involved in metabolism of nitrate and proline at the onset of germination implies their use as sources of nitrogen. Dormant conidia contained transcripts of genes involved in fermentation, gluconeogenesis and the glyoxylate cycle. The presence of such transcripts in dormant conidia may indicate the generation of energy from non-carbohydrate substrates during starvation-induced conidiation or for maintenance purposes during dormancy. The immediate onset of metabolism of internal storage compounds after the onset of germination, and the presence of transcripts of relevant genes, suggest that conidia are primed for the onset of germination.
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Project description:Genome-wide analysis was performed to assess the transcriptional landscape of germinating A. niger conidia using GeneChips. The metabolism of storage compounds during conidial germination was also examined and compared to the transcript levels from associated genes. The transcriptome of dormant conidia was shown to be highly differentiated from that of germinating conidia and major changes in response to environmental shift occurred within the first hour of germination. The breaking of dormancy was associated with increased transcript levels of genes involved in the biosynthesis of proteins, RNA turnover and respiratory metabolism. Increased transcript levels of genes involved in metabolism of nitrate and proline at the onset of germination implies their use as sources of nitrogen. Dormant conidia contained transcripts of genes involved in fermentation, gluconeogenesis and the glyoxylate cycle. The presence of such transcripts in dormant conidia may indicate the generation of energy from non-carbohydrate substrates during starvation-induced conidiation or for maintenance purposes during dormancy. The immediate onset of metabolism of internal storage compounds after the onset of germination, and the presence of transcripts of relevant genes, suggest that conidia are primed for the onset of germination. one biological replicate for each sample, each sample contained pooled RNA from three independent replicates
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