Guenot, Marianne; Loizon, Séverine; Howard, Jennifer; Costa, Giulia; Baker, David A; Mohabeer, Shaneel Y; Troye-Blomberg, Marita; Moreau, Jean-François; Déchanet-Merville, Julie; Mercereau-Puijalon, Odile; +2 more... Mamani-Matsuda, Maria; Behr, Charlotte; (2015) Phosphoantigen Burst upon Plasmodium falciparum Schizont Rupture Can Distantly Activate Vγ9Vδ2 T Cells. Infection and immunity, 83 (10). pp. 3816-3824. ISSN 0019-9567 DOI: https://doi.org/10.1128/IAI.00446-15
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Abstract
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 red blood cells (iRBCs) remains elusive. Here we show that, unlike activation by phosphoantigen-expressing cells, Vγ9Vδ2 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 Vγ9Vδ2 T cells as iRBCs. Bioactivity in the microenvironment is attributable to phosphoantigens, as it is dependent on the parasite DOXP pathway, on Vγ9Vδ2 TCR signaling, and on butyrophilin expression by Vγ9Vδ2 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 Vγ9Vδ2 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 Vγ9Vδ2 T cells that in turn exert remote antiparasitic functions.
Item Type | Article |
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Faculty and Department | Faculty of Infectious and Tropical Diseases > Department of Infection Biology |
PubMed ID | 26169273 |
ISI | 362492600006 |
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