γδ T cells suppress Plasmodium falciparum blood-stage infection by direct killing and phagocytosis

Activated V gamma 9V delta 2 (gamma delta 2) T lymphocytes that sense parasite-produced phosphoantigens are expanded in Plasmodium falciparum-infected patients. Although previous studies suggested that gamma delta 2 T cells help control erythrocytic malaria, whether gamma delta 2 T cells recognize infected red blood cells (iRBCs) was uncertain. Here we show that iRBCs stained for the phosphoantigen sensor butyrophilin 3A1 (BTN3A1). gamma delta 2 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 gamma delta 2 T cell mechanism was identified. In the presence of patient serum, gamma delta 2 T cells phagocytosed and degraded opsonized iRBCs in a CD16-dependent manner, decreasing parasite multiplication. Thus, gamma delta 2 T cells have two ways to control blood-stage malaria-gamma delta T cell antigen receptor (TCR)-mediated degranulation and phagocytosis of antibody-coated iRBCs.

Automated summary

Activated gamma delta 2 T lymphocytes can recognize and lyse infected red blood cells in Plasmodium falciparum-infected patients, controlling blood-stage malaria through both degranulation and phagocytosis mechanisms.