Por favor, use este identificador para citar o enlazar este ítem:
https://www.arca.fiocruz.br/handle/icict/33681
Tipo
ArtículoDerechos de autor
Acceso restringido
Fecha del embargo
2050-01-01
Colecciones
Metadatos
Mostrar el registro completo del ítem
CYTOTOXIC CD8+ T CELLS RECOGNIZE AND KILL PLASMODIUM VIVAX-INFECTED RETICULOCYTES
Autor
Afiliación
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil / Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil.
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Centro de Pesquisas em Medicina Tropical. Porto Velho, RO, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil.
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Plataforma de Medicina Translacional. Ribeirão Preto, SP, Brasil / Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil / Division of Infectious Disease and Immunology. University of Massachusetts Medical School. Worcester, MA, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil.
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Centro de Pesquisas em Medicina Tropical. Porto Velho, RO, Brasil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil.
Program in Cellular and Molecular Medicine. Boston Children’s Hospital and Department of Pediatrics. Harvard Medical School. Boston, MA, USA.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil / Fundação Oswaldo Cruz. Plataforma de Medicina Translacional. Ribeirão Preto, SP, Brasil / Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil / Division of Infectious Disease and Immunology. University of Massachusetts Medical School. Worcester, MA, USA.
Resumen en ingles
Plasmodium vivax causes approximately 100 million clinical malaria cases yearly1,2. The basis of protective immunity is poorly understood and thought to be mediated by antibodies3,4. Cytotoxic CD8+ T cells (CTLs) protect against other intracellular parasites by detecting parasite peptides presented by Human Leukocyte Antigen Class I (HLA-I) on host cells. CTLs kill parasite-infected mammalian cells and intracellular parasites by releasing their cytotoxic granules5,6. Perforin (PFN) delivers the antimicrobial peptide granulysin (GNLY) and death-inducing granzymes (Gzm) into the host cell, and GNLY then delivers Gzms into the parasite. CTLs were thought to have no role against Plasmodium spp. blood stages because red blood cells (RBCs) generally do not express HLA-I7. However, P. vivax infects reticulocytes (Retics) that retain the protein translation machinery. Here we show that P. vivax-infected Retics (iRetic) express HLA-I. Infected patient circulating CD8+ T cells highly express cytotoxic proteins and recognize and form immunological synapses with iRetics in an HLA-dependent manner, releasing their cytotoxic granules to kill both host cell and intracellular parasite, preventing reinvasion. iRetic and parasite killing is PFN-independent, but depends on GNLY, which generally efficiently forms pores only in microbial membranes8. We find that P. vivax depletes cholesterol from the iRetic cell membrane, rendering it GNLY-susceptible. This unexpected T cell defense might be mobilized to improve P. vivax vaccine efficacy.
Compartir