Control of Plasmodium falciparum erythrocytic cycle: γδ T cells target the red blood cell-invasive merozoites
| Autor: | Marita Troye-Blomberg, Iulia Mocan, Franck Halary, Séverine Loizon, Geneviève de Saint-Basile, Jean-François Moreau, Marianne Guenot, Julie Déchanet-Merville, Giulia Costa, Odile Mercereau-Puijalon, Charlotte Behr, Vincent Pitard |
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| Rok vydání: | 2011 |
| Předmět: |
Antigens
Differentiation T-Lymphocyte Erythrocytes T cell T-Lymphocytes Immunology Blotting Western Plasmodium falciparum Schizonts Lymphocyte Activation Biochemistry Host-Parasite Interactions Immunophenotyping Pathogenesis 03 medical and health sciences 0302 clinical medicine Antigen Lysosomal-Associated Membrane Protein 1 parasitic diseases medicine Animals Humans Granulysin Malaria Falciparum Cells Cultured 030304 developmental biology 0303 health sciences Life Cycle Stages biology Merozoites Perforin Receptors Antigen T-Cell gamma-delta Cell Biology Hematology medicine.disease biology.organism_classification Flow Cytometry Virology 3. Good health Red blood cell medicine.anatomical_structure Mutation RNA Interference Malaria 030215 immunology |
| Zdroj: | Blood; Vol 118 |
| ISSN: | 1528-0020 |
| Popis: | The control of Plasmodium falciparum erythrocytic parasite density is essential for protection against malaria, because it prevents pathogenesis and progression toward severe disease. P falciparum blood-stage parasite cultures are inhibited by human Vγ9Vδ2 γδ T cells, but the underlying mechanism remains poorly understood. Here, we show that both intraerythrocytic parasites and the extracellular red blood cell–invasive merozoites specifically activate Vγ9Vδ2 T cells in a γδ T cell receptor–dependent manner and trigger their degranulation. In contrast, the γδ T cell–mediated antiparasitic activity only targets the extracellular merozoites. Using perforin-deficient and granulysin-silenced T-cell lines, we demonstrate that granulysin is essential for the in vitro antiplasmodial process, whereas perforin is dispensable. Patients infected with P falciparum exhibited elevated granulysin plasma levels associated with high levels of granulysin-expressing Vδ2+ T cells endowed with parasite-specific degranulation capacity. This indicates in vivo activation of Vγ9Vδ2 T cells along with granulysin triggering and discharge during primary acute falciparum malaria. Altogether, this work identifies Vγ9Vδ2 T cells as unconventional immune effectors targeting the red blood cell–invasive extracellular P falciparum merozoites and opens novel perspectives for immune interventions harnessing the antiparasitic activity of Vγ9Vδ2 T cells to control parasite density in malaria patients. |
| Databáze: | OpenAIRE |
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