The Journal of infectious diseases · 2026
Cerebrospinal fluid transcriptional immune pathways linked to survival in HIV-associated tuberculous meningitis.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Louine Martineau, Dandekar Ravi, Reddy Sumanth P, Karalius Mary C, Waldrop Greer, Wang Shiyin, Gakuru Jane, Kimuda Sarah, Mugabi Timothy, Musubire Abdu K, Kagimu Enock, Abassi Mahsa, Kabahubya Mable, Williams Darlisha A, Phan Hoang Van, Dai Biyue, Zia Maham, Zorn Kelsey C, Fouassier Camille, Gerungan Chloe, Marra Pedro S, Skipper Caleb P, Bahr Nathan C, Langelier Charles R, Creswell Fiona V, Boulware David R, Meya David B, Wilson Michael R
Аннотация
BACKGROUND: TB meningitis (TBM) has up to 50% mortality in people living with HIV. We investigated differences in cerebrospinal fluid (CSF) host immune responses associated with short-term mortality.
METHODS: We enrolled a prospective cohort of adults with definite, probable and possible HIV-related TBM in Kampala, Uganda. Metagenomic next-generation sequencing (mNGS) of bulk CSF RNA was used to detect co-infecting or alternate CNS pathogens and refine cohort diagnosis. Host transcriptomic profiles from the refined cohort were then compared between 14-day survivors and non-survivors.
RESULTS: CSF mNGS reclassified or excluded 14% of participants based on pathogen detection, yielding 110 participants for transcriptomic analysis, of whom 23% (n=25) died within 14 days. More than 2000 genes were differentially expressed in the CSF based on 14-day mortality (adjusted p-value <0.05). Survivors upregulated T-cell receptor signaling (LCK, FYN, LAT), T-cell survival and differentiation (IL7, CD27, IL12RB1), B-cell receptor signaling (CD81, PLCG2, TNFRSF13C), cytotoxic lymphocyte and NK cell genes (KLRD1, ULBP1), TNF signaling, and class I MHC antigen processing pathways, while downregulating neutrophil chemoattractant CXCL1 and classical complement genes C4A and C4B. Unsupervised clustering identified a hypoinflammatory subgroup with significantly elevated mortality.
CONCLUSIONS: Short-term TBM survival was associated with upregulation of adaptive immunity - including T-cell, B-cell, NK cell, and cytotoxic lymphocyte signaling - alongside TNF signaling and IFN-γ-driven class I MHC antigen processing pathways, with concurrent restraint of complement and neutrophil pathways. This supports investigation of targeted immunomodulatory agents that preserve protective responses while selectively dampening injurious innate pathways, rather than broad immunosuppression with corticosteroids.
METHODS: We enrolled a prospective cohort of adults with definite, probable and possible HIV-related TBM in Kampala, Uganda. Metagenomic next-generation sequencing (mNGS) of bulk CSF RNA was used to detect co-infecting or alternate CNS pathogens and refine cohort diagnosis. Host transcriptomic profiles from the refined cohort were then compared between 14-day survivors and non-survivors.
RESULTS: CSF mNGS reclassified or excluded 14% of participants based on pathogen detection, yielding 110 participants for transcriptomic analysis, of whom 23% (n=25) died within 14 days. More than 2000 genes were differentially expressed in the CSF based on 14-day mortality (adjusted p-value <0.05). Survivors upregulated T-cell receptor signaling (LCK, FYN, LAT), T-cell survival and differentiation (IL7, CD27, IL12RB1), B-cell receptor signaling (CD81, PLCG2, TNFRSF13C), cytotoxic lymphocyte and NK cell genes (KLRD1, ULBP1), TNF signaling, and class I MHC antigen processing pathways, while downregulating neutrophil chemoattractant CXCL1 and classical complement genes C4A and C4B. Unsupervised clustering identified a hypoinflammatory subgroup with significantly elevated mortality.
CONCLUSIONS: Short-term TBM survival was associated with upregulation of adaptive immunity - including T-cell, B-cell, NK cell, and cytotoxic lymphocyte signaling - alongside TNF signaling and IFN-γ-driven class I MHC antigen processing pathways, with concurrent restraint of complement and neutrophil pathways. This supports investigation of targeted immunomodulatory agents that preserve protective responses while selectively dampening injurious innate pathways, rather than broad immunosuppression with corticosteroids.