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

Program in Cellular and Molecular Medicine. Boston Children’s Hospital. USA / Department of Pediatrics. Harvard Medical School. USA / Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Program in Cellular and Molecular Medicine. Boston Children’s Hospital. USA / Department of Pediatrics. Harvard Medical School. USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil.
Department of Pediatrics. Harvard Medical School. USA / Division of Infectious Diseases. Boston Children’s Hospital. USA.
Program in Cellular and Molecular Medicine. Boston Children’s Hospital. USA / Department of Pediatrics. Harvard Medical School. USA.
Program in Cellular and Molecular Medicine. Boston Children’s Hospital. USA / Department of Pediatrics. Harvard Medical School. USA.
Program in Cellular and Molecular Medicine. Boston Children’s Hospital. USA / Department of Pediatrics. Harvard Medical School. USA.
Centro de Pesquisa em Medicina Tropical. Rondônia, RR, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil / Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil / Department of Medicine. University of Massachusetts Medical School. Worcester, MA,USA /F undação Oswaldo Cruz. Instituto René Rachou. Plataforma de Medicina Translacional. Belo Horizonte, MG, Brazil.
Department of Pediatrics. Harvard Medical School. USA / Division of Infectious Diseases. Boston Children’s Hospital. USA.
Program in Cellular and Molecular Medicine. Boston Children’s Hospital. USA / Department of Pediatrics. Harvard Medical School. USA.

Abstract

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.

Keywords

Malaria
γδ T cell
Cytotoxicity
Granulysin
Granzyme
Butyrophilin
Antibody-dependent phagocytosis

Publisher

Nature America Inc.

Citation

JUNQUEIRA, Caroline Furtado et al. γδ T cells suppress Plasmodium falciparum blood-stage infection by direct killing and phagocytosis. Nature Immunology, v. 22, n. 3, p. 347-357, 2021.

DOI

10.1038/s41590-020-00847-4

ISSN

1529-2908

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/59923

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Restricted access

Embargo date

2099-12-31

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