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

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 degranu...

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Autores principales: 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, Mamani-Matsuda, Maria, Behr, Charlotte
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567633/
https://www.ncbi.nlm.nih.gov/pubmed/26169273
http://dx.doi.org/10.1128/IAI.00446-15
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author 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
Mamani-Matsuda, Maria
Behr, Charlotte
author_facet 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
Mamani-Matsuda, Maria
Behr, Charlotte
author_sort Guenot, Marianne
collection PubMed
description 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.
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spelling pubmed-45676332015-09-22 Phosphoantigen Burst upon Plasmodium falciparum Schizont Rupture Can Distantly Activate Vγ9Vδ2 T Cells 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 Mamani-Matsuda, Maria Behr, Charlotte Infect Immun Host Response and Inflammation 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. American Society for Microbiology 2015-09-10 2015-10 /pmc/articles/PMC4567633/ /pubmed/26169273 http://dx.doi.org/10.1128/IAI.00446-15 Text en Copyright © 2015 Guenot et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license (http://creativecommons.org/licenses/by/3.0/) .
spellingShingle Host Response and Inflammation
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
Mamani-Matsuda, Maria
Behr, Charlotte
Phosphoantigen Burst upon Plasmodium falciparum Schizont Rupture Can Distantly Activate Vγ9Vδ2 T Cells
title Phosphoantigen Burst upon Plasmodium falciparum Schizont Rupture Can Distantly Activate Vγ9Vδ2 T Cells
title_full Phosphoantigen Burst upon Plasmodium falciparum Schizont Rupture Can Distantly Activate Vγ9Vδ2 T Cells
title_fullStr Phosphoantigen Burst upon Plasmodium falciparum Schizont Rupture Can Distantly Activate Vγ9Vδ2 T Cells
title_full_unstemmed Phosphoantigen Burst upon Plasmodium falciparum Schizont Rupture Can Distantly Activate Vγ9Vδ2 T Cells
title_short Phosphoantigen Burst upon Plasmodium falciparum Schizont Rupture Can Distantly Activate Vγ9Vδ2 T Cells
title_sort phosphoantigen burst upon plasmodium falciparum schizont rupture can distantly activate vγ9vδ2 t cells
topic Host Response and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567633/
https://www.ncbi.nlm.nih.gov/pubmed/26169273
http://dx.doi.org/10.1128/IAI.00446-15
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