Author | Ataide, Marco Antonio | |
Author | Andrade, Warrison Athanásio Coelho de | |
Author | Zamboni, Dario Simões | |
Author | Wang, Donghai | |
Author | Souza, Maria do Carmo | |
Author | Franklin, Bernardo Simões | |
Author | Elian, Samir | |
Author | Martins, Flaviano dos Santos | |
Author | Pereira, Dhelio | |
Author | Reed, George | |
Author | Fitzgerald, Katherine A. | |
Author | Golenbock, Douglas Taylor | |
Author | Gazzinelli, Ricardo Tostes | |
Access date | 2015-01-28T12:21:41Z | |
Available date | 2015-01-28T12:21:41Z | |
Document date | 2014 | |
Citation | ATAIDE, Marco Antonio, et al. Malaria-Induced NLRP12/NLRP3-Dependent Caspase-1 Activation Mediates Inflammation and Hypersensitivity to Bacterial Superinfection. PLoS Pathog, v. 10, n. 1, p. e1003885, 2014 | pt_BR |
ISSN | 1553-7366 | |
URI | https://www.arca.fiocruz.br/handle/icict/9396 | |
Language | eng | pt_BR |
Publisher | Public Library of Science | pt_BR |
Rights | open access | pt_BR |
Title | Malaria-Induced NLRP12/NLRP3-Dependent Caspase-1 Activation Mediates Inflammation and Hypersensitivity to Bacterial Superinfection | pt_BR |
Type | Article | pt_BR |
DOI | 10.1371/journal.ppat.1003885 | |
Abstract | Cyclic paroxysm and high fever are hallmarks of malaria and are associated with high levels of pyrogenic cytokines, including IL-1β. In this report, we describe a signature for the expression of inflammasome-related genes and caspase-1 activation in malaria. Indeed, when we infected mice, Plasmodium infection was sufficient to promote MyD88-mediated caspase-1 activation, dependent on IFN-γ-priming and the expression of inflammasome components ASC, P2X7R, NLRP3 and/or NLRP12. Pro-IL-1β expression required a second stimulation with LPS and was also dependent on IFN-γ-priming and functional TNFR1. As a consequence of Plasmodium-induced caspase-1 activation, mice produced extremely high levels of IL-1β upon a second microbial stimulus, and became hypersensitive to septic shock. Therapeutic intervention with IL-1 receptor antagonist prevented bacterial-induced lethality in rodents. Similar to mice, we observed a significantly increased frequency of circulating CD14+CD16−Caspase-1+ and CD14dimCD16+Caspase-1+ monocytes in peripheral blood mononuclear cells from febrile malaria patients. These cells readily produced large amounts of IL-1β after stimulation with LPS. Furthermore, we observed the presence of inflammasome complexes in monocytes from malaria patients containing either NLRP3 or NLRP12 pyroptosomes. We conclude that NLRP12/NLRP3-dependent activation of caspase-1 is likely to be a key event in mediating systemic production of IL-1β and hypersensitivity to secondary bacterial infection during malaria | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. 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, United States of America. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. 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, United States of America. | pt_BR |
Affilliation | Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Ribeirão Preto, SP, Brazil. | pt_BR |
Affilliation | University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, United States of America. | pt_BR |
Affilliation | Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Ribeirão Preto, SP, Brazil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil. | pt_BR |
Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil. | pt_BR |
Affilliation | Centro de Pesquisas em Medicina Tropical. Porto Velho, RO, Brazil. | pt_BR |
Affilliation | University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, United States of America. | pt_BR |
Affilliation | University of Massachusetts Medical School. Division of Infectious Diseases and Immunology. Worcester, MA, United States of America. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brasil/University of Massachusetts Medical School. Division of Infectious Diseases and Immunology Worcester, MA, United States of America. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. 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, United States of America. | pt_BR |
Subject | Malaria | pt_BR |
Subject | Plasmodium | pt_BR |
Subject | Inflammasomes | pt_BR |
Subject | Parasitic diseases | pt_BR |
Subject | Monocytes | pt_BR |
Subject | Bacterial pathogens | pt_BR |
Subject | Cytokines | pt_BR |
Subject | Macrophages | pt_BR |