title: Control of Plasmodium falciparum erythrocytic cycle: γδ T cells target the red blood cell-invasive merozoites.
abstract: 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.
authors: Centre National de la Recherche Scientifique, Unité Mixte de Recherche, Bordeaux, France.
authors: Giulia
authors: G
authors: Costa
authors: Séverine
authors: S
authors: Loizon
authors: Marianne
authors: M
authors: Guenot
authors: Iulia
authors: I
authors: Mocan
authors: Franck
authors: F
authors: Halary
authors: Geneviève
authors: G
authors: de Saint-Basile
authors: Vincent
authors: V
authors: Pitard
authors: Julie
authors: J
authors: Déchanet-Merville
authors: Jean-François
authors: JF
authors: Moreau
authors: Marita
authors: M
authors: Troye-Blomberg
authors: Odile
authors: O
authors: Mercereau-Puijalon
authors: Charlotte
authors: C
authors: Behr
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D004912:Erythrocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D005434:Flow Cytometry; D006790:Host-Parasite Interactions / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008018:Life Cycle Stages / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000276:immunology / Q000378:metabolism; D016778:Malaria, Falciparum / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D052940:Merozoites / Q000254:growth & development / Q000276:immunology / Q000502:physiology; D009154:Mutation; D054353:Perforin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology* / Q000502:physiology; D034622:RNA Interference; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D052939:Schizonts / Q000254:growth & development / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C075005:GNLY protein, human; D052118:Lysosomal-Associated Membrane Protein 1; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054353:Perforin