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

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.

Authors: van Laarhoven A, Dian S, van Dorp S, Purnama F, Koeken VACM, Diandini E, Utami F, Livia R, Apriani L, Ardiansyah E, Ter Horst R, Netea MG, Achmad TH, Hill PC, Ruslami R, Alisjahbana B, Ussher JE, Indrati A, Verrall A, Ganiem AR, van Crevel R.
Journal: Sci Rep. 2019 Jan 29;9(1):884
Year: 2019
PubMed: Find in PubMed