Browsing by Author "Santara, Sumit Sen"

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    γδ T cells suppress Plasmodium falciparum blood stage infection by direct killing and phagocytosis
    (Springer Nature, 2021) Junqueira, Caroline; Polidoro, Rafael; Castro, Guilherme; Absalon, Sabrina; Liang, Zhitao; Santara, Sumit Sen; Crespo, Ângela; Pereira, Dhelio B.; Gazzinelli, Ricardo T.; Dvorin, Jeffrey D.; Lieberman, Judy; Pharmacology and Toxicology, School of Medicine
    Activated 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.