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https://www.arca.fiocruz.br/handle/icict/51211
γδ T CELLS SUPPRESS PLASMODIUM FALCIPARUM BLOOD-STAGE INFECTION BY DIRECT KILLING AND PHAGOCYTOSIS
Author
Affilliation
Program in Cellular and Molecular Medicine. Boston Children's Hospital, Boston. MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA/Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Program in Cellular and Molecular Medicine. Boston Children's Hospital, Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Department of Pediatrics. Harvard Medical School. Boston, MA, USA/Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Department of Pediatrics. Harvard Medical School. Boston, MA, USA/Division of Infectious Diseases. Boston Children's Hospital. Boston, MA, USA/Department of Pharmacology and Toxicology. Indiana University School of Medicine. Indianapolis, IN, USA.
Program in Cellular and Molecular Medicine. Boston Children's Hospital, Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Program in Cellular and Molecular Medicine. Boston Children's Hospital, Boston, MA, USA/ Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Program in Cellular and Molecular Medicine. Boston Children's Hospital, Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Centro de Pesquisa em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/Departamento de Bioquímica e Imunologia. Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil/ Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA/Fundação Oswaldo Cruz. Plataforma de Medicina Translacional. Ribeirão Preto, SP, Brazil.
Department of Pediatrics. Harvard Medical School. Boston, MA, USA/Division of Infectious Diseases. Boston Children's Hospital. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children's Hospital. Boston/Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Program in Cellular and Molecular Medicine. Boston Children's Hospital, Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Department of Pediatrics. Harvard Medical School. Boston, MA, USA/Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil.
Department of Pediatrics. Harvard Medical School. Boston, MA, USA/Division of Infectious Diseases. Boston Children's Hospital. Boston, MA, USA/Department of Pharmacology and Toxicology. Indiana University School of Medicine. Indianapolis, IN, USA.
Program in Cellular and Molecular Medicine. Boston Children's Hospital, Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Program in Cellular and Molecular Medicine. Boston Children's Hospital, Boston, MA, USA/ Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Program in Cellular and Molecular Medicine. Boston Children's Hospital, Boston, MA, USA/Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Centro de Pesquisa em Medicina Tropical de Rondônia. Porto Velho, RO, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil/Departamento de Bioquímica e Imunologia. Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil/ Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA/Fundação Oswaldo Cruz. Plataforma de Medicina Translacional. Ribeirão Preto, SP, Brazil.
Department of Pediatrics. Harvard Medical School. Boston, MA, USA/Division of Infectious Diseases. Boston Children's Hospital. Boston, MA, USA
Program in Cellular and Molecular Medicine. Boston Children's Hospital. Boston/Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Abstract
Activated Vγ9Vδ2 (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-γδ T cell antigen receptor (TCR)-mediated degranulation and phagocytosis of antibody-coated iRBCs.
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