Omics · study · 2026
Contribution of cytotoxic CD8 T cells, neutrophils and type 1 interferon signaling to hyperinflammatory pathology in HIV associated TB meningitis [TBM_scRNAseq]
Listed in NCBI GEO
Immune dysregulation contributes to death and disability in tuberculous meningitis.
Description
People living with HIV have the highest risk of TBM, greatest death and disability, and the least evidence that anti-inflammatory therapy improves the poor outcome. Improving therapy relies on a more refined understanding of the host immune response.
Using single-cell RNA sequencing, we characterised 188,983 lumbar CSF cells from 25 adults with HIV-associated TBM and identified correlates of bacterial load. There was heterogeneity in cell composition between patients, but cytotoxic CD8 T cells with low cytokine expression were consistently predominant with a large number expressing GZMK, known to activate complement. In microbiologically-confirmed TBM, there was greater cytotoxicity in T, NK and γδ cells, and higher type 1 interferon stimulation in T and B lymphocytes.
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Neutrophils expressed markers suggesting heightened cytokine stimulation, enhanced effector function, and IL-8-mediated peripheral neutrophil recruitment. In a separate longitudinal cohort, type 1 interferon signalling increased in the blood and CSF following treatment initiation. Overall, findings indicate a hyper-inflammatory immune response in the CSF of HIV-associated TBM patients characterised by an accumulation of granzyme-rich cytotoxic CD8 T cells, highly activated neutrophils and host-detrimental type 1 IFN signalling.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE321nnn/GSE321718 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE321718 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1429325 ncbi.nlm.nih.gov/bioproject/PRJNA1429325 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Longitudinal study 65% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 11 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE321718 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[method].local:method:longitudinal-study | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |