Control of Plasmodium falciparum erythrocytic cycle: gamma-delta T cells target the red blood cell-invasive merozoites
2011 (English)In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 118, no 26, 6952--6962 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2011. Vol. 118, no 26, 6952--6962 p.
IdentifiersURN: urn:nbn:se:su:diva-66401DOI: 10.1182/blood-2011-08-376111ISI: 000298401000033PubMedID: 22045985OAI: oai:DiVA.org:su-66401DiVA: diva2:467741