Dataset Information

Phosphoantigen Burst upon Plasmodium falciparum Schizont Rupture Can Distantly Activate V?9V?2 T Cells.

ABSTRACT: Malaria induces potent activation and expansion of the V?9V?2 subpopulation of ??T cells, which inhibit the Plasmodium falciparum blood cycle through soluble cytotoxic mediators, abrogating merozoite invasion capacity. Intraerythrocytic stages efficiently trigger V?9V?2 T-cell activation and degranulation through poorly understood mechanisms. P. falciparum blood-stage extracts are known to contain phosphoantigens able to stimulate V?9V?2 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, V?9V?2 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 V?9V?2 T cells as iRBCs. Bioactivity in the microenvironment is attributable to phosphoantigens, as it is dependent on the parasite DOXP pathway, on V?9V?2 TCR signaling, and on butyrophilin expression by V?9V?2 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 V?9V?2 T cells, which respond to a few thousand parasites. These data unravel a novel framework, whereby release of phosphoantigens into the extracellular milieu by sequestered parasites likely promotes activation of distant V?9V?2 T cells that in turn exert remote antiparasitic functions.

SUBMITTER: Guenot M

PROVIDER: S-EPMC4567633 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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

Guenot Marianne M Loizon Séverine S Howard Jennifer J Costa Giulia G Baker David A DA Mohabeer Shaneel Y SY Troye-Blomberg Marita M Moreau Jean-François JF Déchanet-Merville Julie J Mercereau-Puijalon Odile O Mamani-Matsuda Maria M Behr Charlotte C

Infection and immunity 20150713 10

Malaria induces potent activation and expansion of the Vγ9Vδ2 subpopulation of γδT cells, which inhibit the Plasmodium falciparum blood cycle through soluble cytotoxic mediators, abrogating merozoite invasion capacity. Intraerythrocytic stages efficiently trigger Vγ9Vδ2 T-cell activation and degranulation through poorly understood mechanisms. P. falciparum blood-stage extracts are known to contain phosphoantigens able to stimulate Vγ9Vδ2 T cells, but how these are presented by intact infected re ...[more]

PMID: 26169273

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Dataset Information

Phosphoantigen Burst upon Plasmodium falciparum Schizont Rupture Can Distantly Activate V?9V?2 T Cells.

Publications

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

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