Astrocytic Alterations Induced by HTLV Type 1-Infected T Lymphocytes: A Role for Tax-1 and Tumor Necrosis Factor α - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue AIDS Research and Human Retroviruses Année : 2000

Astrocytic Alterations Induced by HTLV Type 1-Infected T Lymphocytes: A Role for Tax-1 and Tumor Necrosis Factor α

R. Szymocha
C. Brisson
  • Fonction : Auteur
P. Beurton-Marduel
  • Fonction : Auteur
A. Chalon
  • Fonction : Auteur
A. Bernard
  • Fonction : Auteur
M. Didier-Bazes
  • Fonction : Auteur
M. Belin
  • Fonction : Auteur
P. Giraudon
  • Fonction : Auteur

Résumé

In the neurological disease associated with HTLV-1 infected T lymphocytes infiltrated within the CNS are suspected of playing a prominent role in pathogenesis via inflammatory cytokines and the viral protein Tax-1. We hypothesized that T lymphocytes initiate functional perturbation in astrocytes, resulting in neuronal alteration as glial cells have a crucial role in CNS homeostasis. In particular, astrocytes manage the steady state level of glutamate and continuously provide metabolite precursors to neurons and oligodendrocytes. Using a model system of HTLV-1-infected T cells-astrocytes interaction, we show that after contact with T cells, astrocyte acquire a phenotype typical of gliosis: secretion of proinflammatory cytokines (TNF-alpha, IL-1alpha, IL-6) and matrix metalloproteinases (MMP-9, MMP-3). The concomitant increase in the expression of MMPs and of their endogenous inhibitors (TIMP-1 and TIMP-3) suggests a perturbation in MMP/TIMP balance. This may alter the extracellular matrix and, in turn, the cell environment. At a functional level, glutamate transport and catabolism are impaired in astrocytes. A decrease in glutamate uptake is associated with downregulated expression of glutamate transporters GLAST and GLT1. The expression of astrocytic enzyme of glutamate metabolism is modified with up-regulation of glutamine synthetase and down-regulation of glutamate dehydrogenase. The involvement of Tax-1 in these alterations, directly or indirectly via TNF-alpha, is shown. Altered glutamate uptake and catabolism associated with impairment in cell connectivity via MMP/TIMP imbalance could compromise the functional integrity of the CNS in general and that of neurons and oligodendrocytes in particular.
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Dates et versions

hal-03066695 , version 1 (15-12-2020)

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Citer

R. Szymocha, H. Akaoka, C. Brisson, P. Beurton-Marduel, A. Chalon, et al.. Astrocytic Alterations Induced by HTLV Type 1-Infected T Lymphocytes: A Role for Tax-1 and Tumor Necrosis Factor α. AIDS Research and Human Retroviruses, 2000, 16 (16), pp.1723-1729. ⟨10.1089/08892220050193218⟩. ⟨hal-03066695⟩
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