{"paper_id":"25209645-7a5a-40d0-a0be-7bcb5822ff41","body_text":"Abstract\nImmune dysregulation contributes to death and disability in tuberculous meningitis. People living with HIV have the least evidence that anti-inflammatory therapy improves the poor outcome. Improving therapy relies on a more refined understanding of the host immune response. Single-cell RNA sequencing of 188,983 CSF cells from 25 adults with HIV-associated TBM revealed a predominance of cytotoxic CD8 T cells with low cytokine expression. 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. Neutrophils expressed markers suggesting heightened cytokine stimulation, enhanced effector function, and IL-8-mediated neutrophil recruitment. In a longitudinal cohort, type 1 interferon signaling increased in 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 interferon signaling.\nCompeting Interest Statement\nThe authors have declared no competing interest.\nFootnotes\nManuscript re-formatted with clearer figure legends and figure references in the text. No changes to figures or supplementary materials.\nhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324265\nhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE324044\nhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE321718","source_license":"CC-BY-4.0","license_restricted":false}