Phosphoantigen Burst upon Plasmodium falciparum Schizont Rupture Can Distantly Activate Vγ9Vδ2 T Cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Infection and Immunity Année : 2015

Phosphoantigen Burst upon Plasmodium falciparum Schizont Rupture Can Distantly Activate Vγ9Vδ2 T Cells

Résumé

Malaria induces potent activation and expansion of the V9V2 subpopulation of T cells, which inhibit the Plasmodium fal-ciparum blood cycle through soluble cytotoxic mediators, abrogating merozoite invasion capacity. Intraerythrocytic stages efficiently trigger V9V2 T-cell activation and degranulation through poorly understood mechanisms. P. falciparum blood-stage extracts are known to contain phosphoantigens able to stimulate V9V2 T cells, but how these are presented by intact infected red blood cells (iRBCs) remains elusive. Here we show that, unlike activation by phosphoantigen-expressing cells, V9V2 T-cell activation by intact iRBCs is independent of butyrophilin expression by the iRBC, and contact with an intact iRBC is not required. Moreover, blood-stage culture supernatants proved to be as potent activators of V9V2 T cells as iRBCs. Bioactivity in the microenvironment is attributable to phosphoantigens, as it is dependent on the parasite DOXP pathway, on V9V2 TCR signaling, and on butyrophilin expression by V9V2 T cells. Kinetic studies showed that the phosphoantigens were released at the end of the intraerythrocytic cycle at the time of parasite egress. We document exquisite sensitivity of V9V2 T cells, which respond to a few thousand parasites. These data unravel a novel framework, whereby release of phosphoantigens into the extra-cellular milieu by sequestered parasites likely promotes activation of distant V9V2 T cells that in turn exert remote antipara-sitic functions.
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hal-01777509 , version 1 (24-04-2018)

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Marianne Guenot, Séverine Loizon, Jennifer Howard, Giulia Costa, David A Baker, et al.. Phosphoantigen Burst upon Plasmodium falciparum Schizont Rupture Can Distantly Activate Vγ9Vδ2 T Cells. Infection and Immunity, 2015, 83 (10), pp.3816 - 3824. ⟨10.1128/IAI.00446-15⟩. ⟨hal-01777509⟩

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