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Down-Regulation of Complement Receptors on the Surface of Host Monocyte Even as In Vitro Complement Pathway Blocking Interferes in Dengue Infection

In dengue virus (DENV) infection, complement system (CS) activation appears to have protective and pathogenic effects. In severe dengue fever (DF), the levels of DENV non-structural-1 protein and of the products of complement activation, including C3a, C5a and SC5b-9, are higher before vascular leak...

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Autores principales: Marinho, Cintia Ferreira, Azeredo, Elzinandes Leal, Torrentes-Carvalho, Amanda, Marins-Dos-Santos, Alessandro, Kubelka, Claire Fernandes, de Souza, Luiz José, Cunha, Rivaldo Venâncio, de-Oliveira-Pinto, Luzia Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111305/
https://www.ncbi.nlm.nih.gov/pubmed/25061945
http://dx.doi.org/10.1371/journal.pone.0102014
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author Marinho, Cintia Ferreira
Azeredo, Elzinandes Leal
Torrentes-Carvalho, Amanda
Marins-Dos-Santos, Alessandro
Kubelka, Claire Fernandes
de Souza, Luiz José
Cunha, Rivaldo Venâncio
de-Oliveira-Pinto, Luzia Maria
author_facet Marinho, Cintia Ferreira
Azeredo, Elzinandes Leal
Torrentes-Carvalho, Amanda
Marins-Dos-Santos, Alessandro
Kubelka, Claire Fernandes
de Souza, Luiz José
Cunha, Rivaldo Venâncio
de-Oliveira-Pinto, Luzia Maria
author_sort Marinho, Cintia Ferreira
collection PubMed
description In dengue virus (DENV) infection, complement system (CS) activation appears to have protective and pathogenic effects. In severe dengue fever (DF), the levels of DENV non-structural-1 protein and of the products of complement activation, including C3a, C5a and SC5b-9, are higher before vascular leakage occurs, supporting the hypothesis that complement activation contributes to unfavourable outcomes. The clinical manifestations of DF range from asymptomatic to severe and even fatal. Here, we aimed to characterise CS by their receptors or activation product, in vivo in DF patients and in vitro by DENV-2 stimulation on monocytes. In comparison with healthy controls, DF patients showed lower expression of CR3 (CD11b), CR4 (CD11c) and, CD59 on monocytes. The DF patients who were high producers of SC5b-9 were also those that showed more pronounced bleeding or vascular leakage. Those findings encouraged us to investigate the role of CS in vitro, using monocytes isolated from healthy subjects. Prior blocking with CR3 alone (CD11b) or CR3 (CD11b/CD18) reduced viral infection, as quantified by the levels of intracellular viral antigen expression and soluble DENV non-structural viral protein. However, we found that CR3 alone (CD11b) or CR3 (CD11b/CD18) blocking did not influence major histocompatibility complex presentation neither active caspase-1 on monocytes, thus probably ruling out inflammasome-related mechanisms. Although it did impair the secretion of tumour necrosis factor alpha and interferon alpha. Our data provide strategies of blocking CR3 (CD11b) pathways could have implications for the treatment of viral infection by antiviral-related mechanisms.
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spelling pubmed-41113052014-07-29 Down-Regulation of Complement Receptors on the Surface of Host Monocyte Even as In Vitro Complement Pathway Blocking Interferes in Dengue Infection Marinho, Cintia Ferreira Azeredo, Elzinandes Leal Torrentes-Carvalho, Amanda Marins-Dos-Santos, Alessandro Kubelka, Claire Fernandes de Souza, Luiz José Cunha, Rivaldo Venâncio de-Oliveira-Pinto, Luzia Maria PLoS One Research Article In dengue virus (DENV) infection, complement system (CS) activation appears to have protective and pathogenic effects. In severe dengue fever (DF), the levels of DENV non-structural-1 protein and of the products of complement activation, including C3a, C5a and SC5b-9, are higher before vascular leakage occurs, supporting the hypothesis that complement activation contributes to unfavourable outcomes. The clinical manifestations of DF range from asymptomatic to severe and even fatal. Here, we aimed to characterise CS by their receptors or activation product, in vivo in DF patients and in vitro by DENV-2 stimulation on monocytes. In comparison with healthy controls, DF patients showed lower expression of CR3 (CD11b), CR4 (CD11c) and, CD59 on monocytes. The DF patients who were high producers of SC5b-9 were also those that showed more pronounced bleeding or vascular leakage. Those findings encouraged us to investigate the role of CS in vitro, using monocytes isolated from healthy subjects. Prior blocking with CR3 alone (CD11b) or CR3 (CD11b/CD18) reduced viral infection, as quantified by the levels of intracellular viral antigen expression and soluble DENV non-structural viral protein. However, we found that CR3 alone (CD11b) or CR3 (CD11b/CD18) blocking did not influence major histocompatibility complex presentation neither active caspase-1 on monocytes, thus probably ruling out inflammasome-related mechanisms. Although it did impair the secretion of tumour necrosis factor alpha and interferon alpha. Our data provide strategies of blocking CR3 (CD11b) pathways could have implications for the treatment of viral infection by antiviral-related mechanisms. Public Library of Science 2014-07-25 /pmc/articles/PMC4111305/ /pubmed/25061945 http://dx.doi.org/10.1371/journal.pone.0102014 Text en © 2014 Marinho et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Marinho, Cintia Ferreira
Azeredo, Elzinandes Leal
Torrentes-Carvalho, Amanda
Marins-Dos-Santos, Alessandro
Kubelka, Claire Fernandes
de Souza, Luiz José
Cunha, Rivaldo Venâncio
de-Oliveira-Pinto, Luzia Maria
Down-Regulation of Complement Receptors on the Surface of Host Monocyte Even as In Vitro Complement Pathway Blocking Interferes in Dengue Infection
title Down-Regulation of Complement Receptors on the Surface of Host Monocyte Even as In Vitro Complement Pathway Blocking Interferes in Dengue Infection
title_full Down-Regulation of Complement Receptors on the Surface of Host Monocyte Even as In Vitro Complement Pathway Blocking Interferes in Dengue Infection
title_fullStr Down-Regulation of Complement Receptors on the Surface of Host Monocyte Even as In Vitro Complement Pathway Blocking Interferes in Dengue Infection
title_full_unstemmed Down-Regulation of Complement Receptors on the Surface of Host Monocyte Even as In Vitro Complement Pathway Blocking Interferes in Dengue Infection
title_short Down-Regulation of Complement Receptors on the Surface of Host Monocyte Even as In Vitro Complement Pathway Blocking Interferes in Dengue Infection
title_sort down-regulation of complement receptors on the surface of host monocyte even as in vitro complement pathway blocking interferes in dengue infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111305/
https://www.ncbi.nlm.nih.gov/pubmed/25061945
http://dx.doi.org/10.1371/journal.pone.0102014
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