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

Author(s):Show less -

Junqueira, Caroline ^{[1, 2, 3]} ; Polidoro, Rafael B. ^{[1, 2]} ; Castro, Guilherme ^{[4, 3]} ; Absalon, Sabrina ^{[5, 2, 6]} ; Liang, Zhitao ^{[1, 2]} ; Sen Santara, Sumit ^{[1, 2]} ; Crespo, Angela ^{[1, 2]} ; Pereira, Dhelio B. ^[7] ; Gazzinelli, Ricardo T. ^{[4, 8, 3, 9]} ; Dvorin, Jeffrey D. ^{[2, 6]} ; Lieberman, Judy ^{[1, 2]}

Affiliation

^[1] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 - USA

^[2] Harvard Med Sch, Dept Pediat, Boston, MA 02115 - USA

^[3] Fundacao Oswaldo Cruz, Inst Rene Rachou, Belo Horizonte, MG - Brazil

^[4] Univ Fed Minas Gerais, Dept Bioquim & Imunol, Belo Horizonte, MG - Brazil

^[5] Indiana Univ Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 - USA

^[6] Boston Childrens Hosp, Div Infect Dis, Boston, MA - USA

^[7] Ctr Pesquisa Med Trop Rondonia, Porto Velho, RO - Brazil

^[8] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA - USA

^[9] Fundacao Oswaldo Cruz, Plataforma Med Translac, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: NATURE IMMUNOLOGY; v. 22, n. 3 JAN 2021.
• Web of Science Citations: 1

Abstract

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. (AU)

• FAPESP's process: 16/23618-8 - Immunological mechanisms of resistance and disease in malaria
• Grantee: João Santana da Silva
• Support Opportunities: Research Projects - Thematic Grants