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https://www.arca.fiocruz.br/handle/icict/13541
DNA-CONTAINING IMMUNOCOMPLEXES PROMOTE INFLAMMASOME ASSEMBLY AND RELEASE OF PYROGENIC CYTOKINES BY CD14+ CD16+ CD64HIGH CD32LOW INFLAMMATORY MONOCYTES FROM MALARIA PATIENTS
Autor(es)
Hirako, Isabella Cristina
Marin, Carolina Gallego
Ataide, Marco Antonio Silva
Andrade, Warrison Athanásio Coelho de
Gravina, Humberto Doriguêtto
Rocha, Bruno Coelho
Oliveira, Rosane B. de
Pereira, Dhelio Batista
Vinetz, Joseph
Diamond, Betty
Ram, Sanjay
Golenbock, Douglas Taylor
Gazzinelli, Ricardo Tostes
Marin, Carolina Gallego
Ataide, Marco Antonio Silva
Andrade, Warrison Athanásio Coelho de
Gravina, Humberto Doriguêtto
Rocha, Bruno Coelho
Oliveira, Rosane B. de
Pereira, Dhelio Batista
Vinetz, Joseph
Diamond, Betty
Ram, Sanjay
Golenbock, Douglas Taylor
Gazzinelli, Ricardo Tostes
Afiliação
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil.
University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA / Centro Internacional de Entrenamiento e Investigaciones Medicas. Cali, Colombia.
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil / University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.
University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA.
Centro de Pesquisa em Medicina Tropical. Porto Velho, RO, Brasil.
University of California San Diego. School of Medicine. San Diego, CA, USA.
The Feinstein Institute for Medical Research. Center for Autoimmune and Musculoskeletal Diseases. Manhasset, NY, USA.
University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA.
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil / University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA.
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil / University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.
University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA / Centro Internacional de Entrenamiento e Investigaciones Medicas. Cali, Colombia.
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil / University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA.
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.
University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA.
Centro de Pesquisa em Medicina Tropical. Porto Velho, RO, Brasil.
University of California San Diego. School of Medicine. San Diego, CA, USA.
The Feinstein Institute for Medical Research. Center for Autoimmune and Musculoskeletal Diseases. Manhasset, NY, USA.
University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA.
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil / University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA.
Fundação Oswaldo Cruz. Centro de Pesquisa René Rachou. Belo Horizonte, MG, Brasil / University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, USA / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.
Resumo em Inglês
High levels of circulating immunocomplexes (ICs) are found in patients with either infectious or sterile inflammation. We report that patients with either Plasmodium falciparum or Plasmodium vivax malaria have increased levels of circulating anti-DNA antibodies and ICs containing parasite DNA. Upon stimulation with malaria-induced ICs, monocytes express an NF-κB transcriptional signature. The main source of IC-induced proinflammatory cytokines (i.e., tumor necrosis factor alpha [TNF-α] and interleukin-1β [IL-1β])in peripheral blood mononuclear cells from acute malaria patients was found to be a CD14+ CD16 (FcγRIIIA)+ CD64 (FcγRI)high CD32 (FcγRIIB)low monocyte subset. Monocytes from convalescent patients were predominantly of the classical phenotype (CD14+ CD16−) that produces high levels of IL-10 and lower levels of TNF-α and IL-1β in response to ICs. Finally, we report a novel role for the proinflammatory activity of ICs by demonstrating their ability to induce inflammasome assembly and caspase-1 activation in human monocytes. These findings illuminate our understanding of the pathogenic role of ICs and monocyte subsets and may be relevant for future development of immunity-based interventions with broad applications to systemic inflammatory diseases.
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