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Sci Rep. 2019 Jan 29;9(1):884. doi: 10.1038/s41598-018-36696-3.

Immune cell characteristics and cytokine responses in adult HIV-negative tuberculous meningitis: an observational cohort study.

Author information

1
Radboud University Medical Center, Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Nijmegen, The Netherlands. Arjan.vanLaarhoven@radboudumc.nl.
2
Universitas Padjadjaran, TB-HIV Research Center, Faculty of Medicine, Bandung, Indonesia. Arjan.vanLaarhoven@radboudumc.nl.
3
Radboud University Medical Center, Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Nijmegen, The Netherlands.
4
Universitas Padjadjaran, TB-HIV Research Center, Faculty of Medicine, Bandung, Indonesia.
5
Universitas Padjadjaran, Department of Neurology, Faculty of Medicine/Hasan Sadikin Hospital, Bandung, Indonesia.
6
Radboud University Medical Center, Department of Hematology, Nijmegen, The Netherlands.
7
Human Genomics Laboratory, Craiova University of Medicine and Pharmacy, Craiova, Romania.
8
Universitas Padjadjaran, Department of Biochemistry, Faculty of Medicine, Bandung, Indonesia.
9
Centre for International Health, Universityof Otago, Dunedin, New Zealand.
10
Universitas Padjadjaran, Department of Pharmacology and Therapy, Faculty of Medicine, Bandung, Indonesia.
11
Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.

Abstract

Immunopathology contributes to high mortality in tuberculous meningitis (TBM) but little is known about the blood and cerebrospinal fluid (CSF) immune response. We prospectively characterised the immune response of 160 TBM suspects in an Indonesian cohort, including 67 HIV-negative probable or definite TBM cases. TBM patients presented with severe disease and 38% died in 6 months. Blood from TBM patients analysed by flow cytometry showed lower αβT and γδT cells, NK cells and MAIT cells compared to 26 pulmonary tuberculosis patients (2.4-4-fold, all p < 0.05) and 27 healthy controls (2.7-7.6-fold, p < 0.001), but higher neutrophils and classical monocytes (2.3-3.0-fold, p < 0.001). CSF leukocyte activation was higher than in blood (1.8-9-fold). CSF of TBM patients showed a predominance of αβT and NK cells, associated with better survival. Cytokine production after ex-vivo stimulation of whole blood showed a much broader range in TBM compared to both control groups (p < 0.001). Among TBM patients, high ex-vivo production of TNF-α, IL-6 and IL-10 correlated with fever, lymphocyte count and monocyte HLA-DR expression (all p < 0.05). TBM patients show a strong myeloid blood response, with a broad variation in immune function. This may influence the response to adjuvant treatment and should be considered in future trials of host-directed therapy.

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