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Control of Plasmodium falciparum erythrocytic cycle: gamma-delta T cells target the red blood cell-invasive merozoites
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2011 (Engelska)Ingår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, nr 26, s. 6952--6962Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The control of Plasmodium falciparum erythrocytic parasite density is essential for protection against malaria, as it prevents pathogenesis and progression towards severe disease. P.falciparum blood-stage parasite cultures are inhibited by human Vγ9Vδ2 gamma-delta T cells, but the underlying mechanism remains poorly understood. Here, we show that both intra-erythrocytic 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 anti-parasitic 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 anti-plasmodial 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 anti-parasitic activity of Vγ9Vδ2 T cells to control parasite density in malaria patients.

Ort, förlag, år, upplaga, sidor
2011. Vol. 118, nr 26, s. 6952--6962
Nationell ämneskategori
Immunologi
Identifikatorer
URN: urn:nbn:se:su:diva-66401DOI: 10.1182/blood-2011-08-376111ISI: 000298401000033PubMedID: 22045985OAI: oai:DiVA.org:su-66401DiVA, id: diva2:467741
Tillgänglig från: 2011-12-19 Skapad: 2011-12-19 Senast uppdaterad: 2022-02-24Bibliografiskt granskad

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Troye-Blomberg, Marita

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