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https://www.arca.fiocruz.br/handle/icict/32685
Tipo de documento
ArtigoDireito Autoral
Acesso aberto
Data de embargo
2020-01-01
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PLASMODIUM FALCIPARUM INDUCES TRAINED INNATE IMMUNITY
Autor(es)
Afiliação
Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA.
Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA.
Department of Pediatrics. Rainbow Babies and Children's Hospital. Cleveland, OH, USA.
Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA.
Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA / Corrona. LLC, Southborough, MA, USA.
Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA / Department of Pediatrics. Rainbow Babies and Children's Hospital. Cleveland, OH, USA / Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil.
Department of Internal Medicine and Radboud Center for Infectious Diseases. Radboud University Medical Center. Nijmegen, the Netherlands.
Center for Global Health and Disease. Case Western Reserve University. Cleveland, OH, USA.
Department of Pediatrics. Rainbow Babies and Children's Hospital. Cleveland, OH 44106 / Center for Global Health and Disease, Case Western Reserve University, Cleveland, OH, USA.
Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA.
Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA.
Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA.
Department of Pediatrics. Rainbow Babies and Children's Hospital. Cleveland, OH, USA.
Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA.
Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA / Corrona. LLC, Southborough, MA, USA.
Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA / Department of Pediatrics. Rainbow Babies and Children's Hospital. Cleveland, OH, USA / Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil.
Department of Internal Medicine and Radboud Center for Infectious Diseases. Radboud University Medical Center. Nijmegen, the Netherlands.
Center for Global Health and Disease. Case Western Reserve University. Cleveland, OH, USA.
Department of Pediatrics. Rainbow Babies and Children's Hospital. Cleveland, OH 44106 / Center for Global Health and Disease, Case Western Reserve University, Cleveland, OH, USA.
Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA.
Department of Medicine. University of Massachusetts Medical School. Worcester, MA, USA.
Resumo em Inglês
Malarial infection in naive individuals induces a robust innate immune response. In the recently described model of innate immune memory, an initial stimulus primes the innate immune system to either hyperrespond (termed training) or hyporespond (tolerance) to subsequent immune challenge. Previous work in both mice and humans demonstrated that infection with malaria can both serve as a priming stimulus and promote tolerance to subsequent infection. In this study, we demonstrate that initial stimulation with Plasmodium falciparum-infected RBCs or the malaria crystal hemozoin induced human adherent PBMCs to hyperrespond to subsequent ligation of TLR2. This hyperresponsiveness correlated with increased H3K4me3 at important immunometabolic promoters, and these epigenetic modifications were also seen in Kenyan children naturally infected with malaria. However, the use of epigenetic and metabolic inhibitors indicated that the induction of trained immunity by malaria and its ligands may occur via a previously unrecognized mechanism(s).
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