Functional changes in astrocytes by human T-lymphotropic virus type-1 T-lymphocytes.
The human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of a chronic progressive myelopathy (TSP/HAM) in which lesions of the central nervous system (CNS) are associated with infiltration of HTLV-1-infected T-cells. In a model that mimics the interaction between glial and T-cells, we show that transient contact with T-lymphocytes chronically infected with HTLV-1 induce profound metabolic alterations in astrocytes. Within the first week post-contact, an overall activation of astrocyte metabolism was observed as assessed by enhanced uptake of glutamate and glucose, and lactate release. In contrast, longer examination showed a reduced astrocytic accumulation of glutamate. The time course of the change in glutamate uptake was in fact biphasic. Previous observations indicated that HTLV-1 protein Tax-1 was involved in this delayed decrease, via the induction of TNF-alpha. The expression of the glial glutamate transporters, GLAST and GLT-1 decreased in parallel. These decreases in glutamate uptake and transporters' expression were associated with an imbalance in the expression of the catabolic enzymes of glutamate, GS and GDH, presumably due to Tax-1. Given the fact that impairment of glutamate management in astrocytes is able to compromise the functional integrity of neurons and oligodendrocytes, our results altogether give new insights into the physiopathology of TSP/HAM.
Akaoka
H
H
Faculte de Medecine Laennec, Experimental Neurobiology and Physiopathology, INSERM U433, F69372 Cedex 08, Lyon, France.
Szymocha
R
R
Beurton-Marduel
P
P
Bernard
A
A
Belin
M F
MF
Giraudon
P
P
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D002450:Cell Communication; D002460:Cell Line; D018920:Coculture Techniques; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D015368:Human T-lymphotropic virus 1; D019344:Lactic Acid / Q000378:metabolism; D051381:Rats; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D013997:Time Factors
D019344:Lactic Acid; D018698:Glutamic Acid; D005947:Glucose