Tuberculous meningitis in children is characterized by compartmentalized immune responses and neural excitotoxicity
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Tuberculous meningitis (TBM) is the most severe form of TB with high rates of mortality and morbidity. We conducted RNA-sequencing on whole blood as well as on ventricular and lumbar cerebrospinal fluid (CSF) of pediatric patients treated for TBM. Differential transcript expression of TBM cases were compared with healthy controls in whole blood and with non-TB cerebral infection controls in CSF. Whole blood RNA-Seq analysis demonstratesa distinct immune response pattern in TBM, with significant increase inboth canonical and non-canonical inflammasome activation and decrease in T-cell activation. In ventricular CSF, a significant enrichment associated with neuronal excitotoxicity and cerebral damage is detected in TBM. Finally, compartmental comparison in TBM indicatesthat the ventricular profile representsbrain injury whereas the lumbar profile representsprotein translation and cytokine signalling. Together, transcriptomic analysis shows thatdisease processes differ between the periphery and the central nervous system, and within brain compartments.
Date Issued
2019-08-21
Date Acceptance
2019-08-06
Citation
Nature Communications, 2019, 10
ISSN
2041-1723
Publisher
Nature Research (part of Springer Nature)
Journal / Book Title
Nature Communications
Volume
10
Copyright Statement
This article is licensed under a Creative CommonsAttribution 4.0 International License, which permits use, sharing,adaptation, distribution and reproduction in any medium or format, as long as you giveappropriate credit to the original author(s) and the source, provide a link to the CreativeCommons license, and indicate if changes were made. The images or other third partymaterial in this article are included in the article’s Creative Commons license, unlessindicated otherwise in a credit line to the material. If material is not included in thearticle’s Creative Commons license and your intended use is not permitted by statutoryregulation or exceeds the permitted use, you will need to obtain permission directly fromthe copyright holder. To view a copy of this license, visithttp://creativecommons.org/licenses/by/4.0/
Sponsor
Medical Research Council (MRC)
Wellcome Trust
Grant Number
MR/R008922/1
104803/Z/14/Z
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CEREBROSPINAL-FLUID
EXPRESSION
GLUTAMATE
DEXAMETHASONE
PROTEINS
Publication Status
Published
Article Number
ARTN 3767
Date Publish Online
2019-08-21