Document Detail

Control of Plasmodium falciparum erythrocytic cycle: gamma-delta T cells target the red blood cell-invasive merozoites.
MedLine Citation:
PMID:  22045985     Owner:  NLM     Status:  Publisher    
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.
Giulia Costa; Séverine Loizon; Marianne Guenot; Iulia Mocan; Franck Halary; Geneviève de Saint-Basile; Vincent Pitard; Julie Déchanet-Merville; Jean-François Moreau; Marita Troye-Blomberg; Odile Mercereau-Puijalon; Charlotte Behr
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-1
Journal Detail:
Title:  Blood     Volume:  -     ISSN:  1528-0020     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
CNRS, UMR 5164, Bordeaux, France;
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