Perfil de resposta imunológica inata de pacientes infectados pelo vírus Zika
The receptors of the innate immunity, mainly Toll like receptors (TLRs) and RIG like receptors (RLRs) are important molecules for the initial recognition of Zika virus and modulation of protective immune response with production of type 1 IFN. Recent Zika virus epidemics presented the main conseq...
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Vírus Zika Receptores de reconhecimento de padrões Imunidade inata CNPQ::CIENCIAS BIOLOGICAS: BIOLOGIA PARASITÁRIA |
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Vírus Zika Receptores de reconhecimento de padrões Imunidade inata CNPQ::CIENCIAS BIOLOGICAS: BIOLOGIA PARASITÁRIA Silva, Marcelo Henrique Matias da Perfil de resposta imunológica inata de pacientes infectados pelo vírus Zika |
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The receptors of the innate immunity, mainly Toll like receptors (TLRs) and RIG like
receptors (RLRs) are important molecules for the initial recognition of Zika virus and
modulation of protective immune response with production of type 1 IFN. Recent Zika
virus epidemics presented the main consequences the increase in the number of
cases of Guillain-Barré syndrome and the emergence of congenital Zika syndrome,
which may result in microcephaly and other neurological damage. Immunological
mechanisms that confer protection or pathology during infection by this virus have
not yet been elucidated. Thus, the aim of the present study was to evaluate the
profile of the innate immune response in patients during acute Zika virus infection.
For this, the expression of messenger RNA (TLR3, TLR7, TLR8, TLR9), RLR MDA-5
(Melanoma Differentiation-Associated protein 5), TRIF adapter molecules (Toll / IL-1
Receptor (IFN-γ) and cytokines (IL-6, IL-12, IFN-α, TNF-α, IFN-γ and IFN-γ).
Peripheral blood mononuclear cells (PBMC) from 30 patients with symptoms of acute
Zika virus infection with diagnosis confirmed by real-time RT-PCR (qRT-PCR) and
nine uninfected healthy individuals were used to quantify the immune response
profile. Patients with acute Zika virus infection had high expression of TLR3, IFN-α,
IFN-β and IFN-γ when compared to healthy controls. In addition, there was a positive
correlation between TLR3 expression in relation to IFN-α and IFN-β. On the other
hand, patients infected by zika virus showed reduced expression of TLR8, Myd88
and TNF-α. Similar expression of TLR7, TLR9, MDA-5, TRIF, IL-6 and IL-12 was
observed between the group of patients infected with zika virus and control subjects.
Our results indicate that acute infection (up to 5 days after the onset of symptoms) by
the Zika virus induces the production of IFN-γ, IFN-α and IFN-β, mainly via TLR3-
dependent pathway. However, patients infected by the zika virus showed a reduction
in the expression of TLR8, Myd88 and TNF-α, molecules also involved in antiviral
immunity. |
author2 |
Fernandes, José Verissimo |
author_facet |
Fernandes, José Verissimo Silva, Marcelo Henrique Matias da |
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masterThesis |
author |
Silva, Marcelo Henrique Matias da |
author_sort |
Silva, Marcelo Henrique Matias da |
title |
Perfil de resposta imunológica inata de pacientes infectados pelo vírus Zika |
title_short |
Perfil de resposta imunológica inata de pacientes infectados pelo vírus Zika |
title_full |
Perfil de resposta imunológica inata de pacientes infectados pelo vírus Zika |
title_fullStr |
Perfil de resposta imunológica inata de pacientes infectados pelo vírus Zika |
title_full_unstemmed |
Perfil de resposta imunológica inata de pacientes infectados pelo vírus Zika |
title_sort |
perfil de resposta imunológica inata de pacientes infectados pelo vírus zika |
publisher |
Brasil |
publishDate |
2018 |
url |
https://repositorio.ufrn.br/jspui/handle/123456789/26354 |
work_keys_str_mv |
AT silvamarcelohenriquematiasda perfilderespostaimunologicainatadepacientesinfectadospeloviruszika |
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1773961056437141504 |
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ri-123456789-263542019-01-30T16:49:12Z Perfil de resposta imunológica inata de pacientes infectados pelo vírus Zika Silva, Marcelo Henrique Matias da Fernandes, José Verissimo Guedes, Paulo Marcos da Matta Araújo, Joselio Maria Galvão de Nascimento, Manuela Sales Lima Vírus Zika Receptores de reconhecimento de padrões Imunidade inata CNPQ::CIENCIAS BIOLOGICAS: BIOLOGIA PARASITÁRIA The receptors of the innate immunity, mainly Toll like receptors (TLRs) and RIG like receptors (RLRs) are important molecules for the initial recognition of Zika virus and modulation of protective immune response with production of type 1 IFN. Recent Zika virus epidemics presented the main consequences the increase in the number of cases of Guillain-Barré syndrome and the emergence of congenital Zika syndrome, which may result in microcephaly and other neurological damage. Immunological mechanisms that confer protection or pathology during infection by this virus have not yet been elucidated. Thus, the aim of the present study was to evaluate the profile of the innate immune response in patients during acute Zika virus infection. For this, the expression of messenger RNA (TLR3, TLR7, TLR8, TLR9), RLR MDA-5 (Melanoma Differentiation-Associated protein 5), TRIF adapter molecules (Toll / IL-1 Receptor (IFN-γ) and cytokines (IL-6, IL-12, IFN-α, TNF-α, IFN-γ and IFN-γ). Peripheral blood mononuclear cells (PBMC) from 30 patients with symptoms of acute Zika virus infection with diagnosis confirmed by real-time RT-PCR (qRT-PCR) and nine uninfected healthy individuals were used to quantify the immune response profile. Patients with acute Zika virus infection had high expression of TLR3, IFN-α, IFN-β and IFN-γ when compared to healthy controls. In addition, there was a positive correlation between TLR3 expression in relation to IFN-α and IFN-β. On the other hand, patients infected by zika virus showed reduced expression of TLR8, Myd88 and TNF-α. Similar expression of TLR7, TLR9, MDA-5, TRIF, IL-6 and IL-12 was observed between the group of patients infected with zika virus and control subjects. Our results indicate that acute infection (up to 5 days after the onset of symptoms) by the Zika virus induces the production of IFN-γ, IFN-α and IFN-β, mainly via TLR3- dependent pathway. However, patients infected by the zika virus showed a reduction in the expression of TLR8, Myd88 and TNF-α, molecules also involved in antiviral immunity. Os receptores da imunidade inata, principalmente receptores do tipo toll (TLRs) e receptores do tipo Rig (RLRs) são moléculas importantes para o reconhecimento inicial do vírus Zika e modulação de resposta imunológica protetora com produção de IFN do tipo 1. Epidemias recentes pelo vírus Zika apresentaram como principais consequências o aumento do número de casos da síndrome de Guillain-Barré e o surgimento da síndrome congênita do vírus Zika que pode resultar em microcefalia e outros danos neurológicos. Os mecanismos imunológicos que conferem proteção ou patologia durante a infecção por esse vírus ainda não foram elucidados. Dessa forma, o objetivo do presente estudo foi avaliar o perfil da resposta imunológica inata em pacientes durante a infecção aguda pelo vírus Zika. Para isso, foi quantificada a expressão de RNA mensageiro (RNAm) dos TLRs (TLR3, TLR7, TLR8, TLR9), do RLR MDA-5 (Melanoma Differentiation-Associated protein 5), das moléculas adaptadoras TRIF (Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-β) e Myd88 (Myeloid Differentiation Primary Response Gene 88) e das citocinas (IL-6, IL12, IFN-α, TNF-α, IFN-β, IFN-γ). Células mononucleares do sangue periférico (PBMC) de 30 pacientes com sintomas da infecção aguda pelo vírus Zika com diagnóstico confirmado por RT-PCR em tempo real (qRT-PCR) e de nove indivíduos saudáveis não infectados foram utilizadas para quantificação do perfil de resposta imunológica. Pacientes com infecção aguda pelo vírus Zika apresentaram elevada expressão de TLR3, IFN-α, IFN-β e IFN-γ, quando comparado aos controles saudáveis. Ademais, houve correlação positiva entre a expressão de TLR3 em relação a IFN-α e IFN-β. Por outro lado, pacientes infectados pelo vírus zika apresentaram redução na expressão de TLR8, Myd88 e TNF-α. Foi observada expressão semelhante de TLR7, TLR9, MDA-5, TRIF, IL-6 e IL-12 entre o grupo de pacientes infectados pelo vírus zika e indivíduos do grupo controle. Nossos resultados indicam que a infecção aguda (até 5 dias após o aparecimento dos sintomas) pelo vírus Zika induz a produção de IFN-γ, IFN-α e IFN-β, principalmente por via dependente de TLR3. Por outro lado, os pacientes infectados pelo vírus zika apresentaram uma redução da expressão de TLR8, Myd88 e TNF-α, moléculas também envolvidas na imunidade antiviral. 2018-12-13T21:58:54Z 2018-12-13T21:58:54Z 2018-03-02 masterThesis SILVA, Marcelo Henrique Matias da. Perfil de resposta imunológica inata de pacientes infectados pelo vírus Zika. 2018. 58f. Dissertação (Mestrado em Biologia Parasitária) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2018. https://repositorio.ufrn.br/jspui/handle/123456789/26354 por Acesso Aberto application/pdf Brasil UFRN PROGRAMA DE PÓS-GRADUAÇÃO EM BIOLOGIA PARASITÁRIA |