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Single-cell RNA sequencing reveals the diversity of the immunological landscape in response to murine coronavirus infection of the central nervous system

ABSTRACT: Single-cell RNA sequencing reveals the diversity of the immunological landscape in response to murine coronavirus infection of the central nervous system

PROVIDER: PRJNA664700 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12681865.fastq.gz	Fastqsanger.gz
	SRR12681866.fastq.gz	Fastqsanger.gz
	SRR12681867.fastq.gz	Fastqsanger.gz
	SRR12681868.fastq.gz	Fastqsanger.gz
	SRR12681869.fastq.gz	Fastqsanger.gz

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Tumor cells impair immunological synapse formation via central nervous system-enriched metabolite

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Tumor cells impair immunological synapse formation via central nervous system-enriched metabolite

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Single-cell RNA sequencing reveals the diversity of the immunological landscape in response to murine coronavirus infection of the central nervous system

Project description:Intracranial (i.c.) infection of susceptible C57BL/6 mice with a neurotropic JHM strain mouse hepatitis virus (a member of the Coronaviridae family) results in acute encephalomyelitis and viral persistence associated with an immune-mediated demyelinating disease. The present study was undertaken to better understand the molecular pathways evoked during innate and adaptive immune responses as well as the chronic demyelinating stage of disease in response to JHMV infection of the central nervous system (CNS). Using single cell RNA sequencing analysis (scRNAseq) on flow-sorted CD45-positive cells (CD45+) enriched from brains and spinal cords of experimental mice, we demonstrate the heterogeneity of the immune response as determined by unique molecular signatures and pathways involved in effective anti-viral host defense. Furthermore, we identify potential genes involved in contributing to demyelination as well as remyelination being expressed by both microglia and macrophages. Collectively, these findings emphasize the diversity of the immune response and molecular networks at defined stages following viral infection of the CNS.

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Microglia influence host defense, disease, and repair following coronavirus infection of the central nervous system

Project description:The present study examines functional contributions of microglia in host defense, demyelination, and remyelination following infection of susceptible mice with a neurotropic coronavirus. Treatment with PLX5622, an inhibitor of colony stimulating factor 1 receptor (CSF1R) that efficiently depletes microglia, prior to infection of the central nervous system (CNS) with the neurotropic JHM strain of mouse hepatitis virus (JHMV) resulted in increased mortality compared with control mice that correlated with impaired control of viral replication. Single cell RNA sequencing (scRNASeq) of CD45+ cells isolated from the CNS revealed that PLX5622 treatment resulted in muted CD4+ T cell activation profile that was associated with decreased expression of transcripts encoding MHC class II and CD86 in macrophages but not dendritic cells. Evaluation of spinal cord demyelination revealed a marked increase in white matter damage in PLX5622‐treated mice that corresponded with elevated expression of transcripts encoding disease‐associated proteins Osteopontin (Spp1), Apolipoprotein E (Apoe), and Triggering receptor expressed on myeloid cells 2 (Trem2) that were enriched within macrophages. In addition, PLX5622 treatment dampened expression of Cystatin F (Cst7), Insulin growth factor 1 (Igf1), and lipoprotein lipase (Lpl) within macrophage populations which have been implicated in promoting repair of damaged nerve tissue and this was associated with impaired remyelination. Collectively, these findings argue that microglia tailor the CNS microenvironment to enhance control of coronavirus replication as well as dampen the severity of demyelination and influence repair.

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Iodine I 131 Monoclonal Antibody 3F8 in Treating Patients With Central Nervous System Cancer or Leptomeningeal Cancer

Project description:RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody 3F8, can find tumor cells and carry tumor-killing substances to them without harming normal cells. This may be an effective treatment for central nervous system cancer or leptomeningeal metastases. PURPOSE: This phase II trial is studying the side effects and how well iodine I 131 monoclonal antibody 3F8 works in treating patients with central nervous system cancer or leptomeningeal cancer.

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Tumor cells impair immunological synapse formation via central nervous system-enriched metabolite

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Microglia influence host defense, disease, and repair following coronavirus infection of the central nervous system

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Project description:Genomic aberrations in primary central nervous system lymphoma (PCNSL). Two-condition experiment, PCNSLs vs. healthy men. Biological replicates: 12 tumors replicates, 13 peripheral blood replicates.

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