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Control of Plasmodium falciparum erythrocytic cycle: gamma-delta T cells target the red blood cell-invasive merozoites
Vise andre og tillknytning
2011 (engelsk)Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, nr 26, s. 6952--6962Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
2011. Vol. 118, nr 26, s. 6952--6962
HSV kategori
Identifikatorer
URN: urn:nbn:se:su:diva-66401DOI: 10.1182/blood-2011-08-376111ISI: 000298401000033PubMedID: 22045985OAI: oai:DiVA.org:su-66401DiVA, id: diva2:467741
Tilgjengelig fra: 2011-12-19 Laget: 2011-12-19 Sist oppdatert: 2017-12-08bibliografisk kontrollert

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