Junqueira, CarolinePolidoro, RafaelCastro, GuilhermeAbsalon, SabrinaLiang, ZhitaoSantara, Sumit SenCrespo, ÂngelaPereira, Dhelio B.Gazzinelli, Ricardo T.Dvorin, Jeffrey D.Lieberman, Judy2024-08-122024-08-122021Junqueira C, Polidoro RB, Castro G, et al. γδ T cells suppress Plasmodium falciparum blood-stage infection by direct killing and phagocytosis. Nat Immunol. 2021;22(3):347-357. doi:10.1038/s41590-020-00847-4https://hdl.handle.net/1805/42728Activated Vγδ9Vδ2 (γδ2) T lymphocytes that sense parasite-produced phosphoantigens are expanded in Plasmodium falciparum-infected patients. Although previous studies suggested that γδ2 T cells help control erythrocytic malaria, whether γδ2 T cells recognize infected red blood cells (iRBCs) was uncertain. Here we show that iRBCs stained for the phosphoantigen sensor, butyrophilin 3A1 (BTN3A1). γδ2 T cells formed immune synapses and lysed iRBCs in a contact, phosphoantigen, BTN3A1 and degranulation-dependent manner, killing intracellular parasites. Granulysin released into the synapse lysed iRBCs and delivered death-inducing granzymes to the parasite. All intra-erythrocytic parasites were susceptible, but schizonts were most sensitive. A second protective γδ2 T cell mechanism was identified. In the presence of patient serum, γδ2 T cells phagocytosed and degraded opsonized iRBCs in a CD16-dependent manner, decreasing parasite multiplication. Thus, γδ2 T cells have two ways to control blood stage malaria – γδT cell antigen receptor (TCR)-mediated degranulation and phagocytosis of antibody-coated iRBCs.en-USPublisher PolicyMalariaγδ T cellCytotoxicityGranulysinGranzymeButyrophilinAntibody-dependent phagocytosisArticle