Avaliação da resposta imune de neonatos não infectados pelo HIV-1 nascidos de gestantes soropositivas

Detalhes bibliográficos
Autor(a) principal: Machado, Joana Hygino da Silva
Data de Publicação: 2009
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
Texto Completo: http://www.bdtd.uerj.br/handle/1/14426
Resumo: The acquired immunodeficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV), is one the most destructive epidemic in the world, and the HIV-infection in young women has been increasing fast in the recent times. This fact has an important impact on vertical virus transmission. Although the great majority of the pediatric AIDS cases all over the world results from vertical transmission, approximately two thirds of the children exposed to the HIV during the fetal life are not infected by the virus. Many works suggest that during pregnancy, maternal infectious diseases could have complex consequences to the fetus development, and few works have explored the impact of HIV exposition on immunological responsiveness of uninfected children to different stimuli, particularly in the era of the anti-retroviral drugs. Therefore, this work aimed to evaluate immune events in HIV-1-exposed uninfected neonates born from pregnant women who controlled (G1) or not (G2) the plasma viral load, using unexposed neonates as control. Cord blood from each neonate was collected, plasma and mononuclear cells were separated and the lymphoproliferation and cytokine pattern were evaluated. The results demonstrated that the in vitro lymphoproliferation induced by polyclonal activators was higher in the G2 neonates. Nevertheless, no cell culture responded to poll synthetic HIV-1 envelope peptides. The cytokine dosage in the plasma and supernatants of polyclonally-activated cultures demonstrated that, while IL-4 and IL-10 were the dominant cytokines produced in G1 and control groups, the secretion of IFN-γ, IL-1, Il-6, IL-17 and TNF-α was significantly higher in G2 neonates. Systemic levels of IL-10 observed among the G1 neonates were higher in those born from mothers treated with viral transcriptase reverse inhibitors drugs. On the other hand, higher levels of inflammatory cytokines were observed among them born from pregnant women treated with highly active anti-retroviral therapy. In summary, our results indicate an altered immune responsiveness in neonates exposed in utero to HIV and support the role of maternal anti-viral treatment with less potent drugs to attenuate it.
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spelling Andrade, Arnaldo Feitosa Braga dehttp://lattes.cnpq.br/7193213149282123Bento, Cleonice Alves de Melohttp://lattes.cnpq.br/6829909822082760Milagres, Lucimar Gonçalveshttp://lattes.cnpq.br/0636353193914166Costilla, Landi Veivi Guillermohttp://lattes.cnpq.br/4761718254591930Maximiano, Elisabeth Santoshttp://lattes.cnpq.br/5489217243902505http://lattes.cnpq.br/0223224432356842Machado, Joana Hygino da Silva2021-01-07T15:16:24Z2015-02-122009-08-07http://www.bdtd.uerj.br/handle/1/14426The acquired immunodeficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV), is one the most destructive epidemic in the world, and the HIV-infection in young women has been increasing fast in the recent times. This fact has an important impact on vertical virus transmission. Although the great majority of the pediatric AIDS cases all over the world results from vertical transmission, approximately two thirds of the children exposed to the HIV during the fetal life are not infected by the virus. Many works suggest that during pregnancy, maternal infectious diseases could have complex consequences to the fetus development, and few works have explored the impact of HIV exposition on immunological responsiveness of uninfected children to different stimuli, particularly in the era of the anti-retroviral drugs. Therefore, this work aimed to evaluate immune events in HIV-1-exposed uninfected neonates born from pregnant women who controlled (G1) or not (G2) the plasma viral load, using unexposed neonates as control. Cord blood from each neonate was collected, plasma and mononuclear cells were separated and the lymphoproliferation and cytokine pattern were evaluated. The results demonstrated that the in vitro lymphoproliferation induced by polyclonal activators was higher in the G2 neonates. Nevertheless, no cell culture responded to poll synthetic HIV-1 envelope peptides. The cytokine dosage in the plasma and supernatants of polyclonally-activated cultures demonstrated that, while IL-4 and IL-10 were the dominant cytokines produced in G1 and control groups, the secretion of IFN-γ, IL-1, Il-6, IL-17 and TNF-α was significantly higher in G2 neonates. Systemic levels of IL-10 observed among the G1 neonates were higher in those born from mothers treated with viral transcriptase reverse inhibitors drugs. On the other hand, higher levels of inflammatory cytokines were observed among them born from pregnant women treated with highly active anti-retroviral therapy. In summary, our results indicate an altered immune responsiveness in neonates exposed in utero to HIV and support the role of maternal anti-viral treatment with less potent drugs to attenuate it.A síndrome da imunodeficiência adquirida (AIDS), causada pelo vírus da imunodeficiência humana (HIV), é uma das mais destrutivas epidemias do mundo, e a infecção pelo HIV em mulheres jovens vem aumentando rapidamente nos dias atuais. Esse fato tem um impacto importante na transmissão vertical do vírus. Apesar da grande maioria dos casos de aids pediátrica em todo mundo resultar da transmissão vertical, aproximadamente dois terços das crianças expostas ao HIV durante a vida fetal não são infectadas pelo vírus. Muitos trabalhos sugerem que durante a gestação doenças infecciosas maternas podem ter consequências complexas para o desenvolvimento do feto, e poucos trabalhos têm explorado o impacto da exposição ao HIV sobre a responsividade imunológica de crianças não infectadas a diferentes estímulos, particularmente na era das drogas antirretrovirais. Portanto, esse trabalho teve como objetivo avaliar eventos imunes em neonatos não-infectados expostos ao HIV-1 nascidos de gestantes que controlam (G1) ou não (G2) a carga viral plasmática, usando neonatos não expostos como controle. Para tanto, sangue do cordão umbilical de cada neonato foi coletado, plasma e células mononucleares foram separados e a linfoproliferação e o perfil de citocinas foram avaliados. Os resultados demonstraram que a linfoproliferação in vitro induzido por ativadores policlonais foi maior nos neonatos do G2. Entretanto, nenhuma cultura de célula respondeu a um conjunto de peptídeos sintéticos do envelope do HIV-1. A dosagem de citocinas no plasma e nos sobrenadantes das culturas ativadas policlonalmente demonstrou que, enquanto a IL-4 e IL-10 foram as citocinas dominantes produzidas nos grupos G1 e controle, a secreção de IFN-γ, IL-1, Il-6, IL-17 e TNF-α foi significativamente superior nos neonatos G2. Níveis sistêmicos de IL-10 observados dentre os neonatos G1 foram maiores naqueles nascidos de mães tratadas com drogas inibidoras da transcriptase reversa do vírus. Por outro lado, níveis superiores de citocinas inflamatórias foram observados dentre estes nascidos de gestantes tratadas com terapia antirretroviral de alta eficácia. Em resumo, nossos resultados indicam uma responsividade imune alterada em neonatos expostos in utero ao HIV-1 e reforça o papel do tratamento materno anti-viral com drogas menos potentes em atenuar tais distúrbios.Submitted by Boris Flegr (boris@uerj.br) on 2021-01-07T15:16:24Z No. of bitstreams: 1 DISSERTACAO_FINAL_PUBLICADA_Joana_Hygino_da_Silva_Machado.pdf: 6262238 bytes, checksum: b46c2c5e77f11055813a9ac2a8450b60 (MD5)Made available in DSpace on 2021-01-07T15:16:24Z (GMT). No. of bitstreams: 1 DISSERTACAO_FINAL_PUBLICADA_Joana_Hygino_da_Silva_Machado.pdf: 6262238 bytes, checksum: b46c2c5e77f11055813a9ac2a8450b60 (MD5) Previous issue date: 2009-08-07Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em MicrobiologiaUERJBRCentro Biomédico::Faculdade de Ciências MédicasHIV-1AIDSNeonatesAnti-retroviralLymphoproliferationCytokineHIV-1AidsNeonatosAnti-retroviralLinfoproliferaçãoCitocinasHIV-1HIV (Vírus)Infecções por HIVAIDS (Doença)Agentes antirretroviraisCitocinasCNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIAAvaliação da resposta imune de neonatos não infectados pelo HIV-1 nascidos de gestantes soropositivasEvaluation of immune response in HIV-1-exposed uninfected neonates born from seropositive pregnant womeninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALDISSERTACAO_FINAL_PUBLICADA_Joana_Hygino_da_Silva_Machado.pdfapplication/pdf6262238http://www.bdtd.uerj.br/bitstream/1/14426/1/DISSERTACAO_FINAL_PUBLICADA_Joana_Hygino_da_Silva_Machado.pdfb46c2c5e77f11055813a9ac2a8450b60MD511/144262024-02-26 19:54:42.862oai:www.bdtd.uerj.br:1/14426Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032024-02-26T22:54:42Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false
dc.title.por.fl_str_mv Avaliação da resposta imune de neonatos não infectados pelo HIV-1 nascidos de gestantes soropositivas
dc.title.alternative.eng.fl_str_mv Evaluation of immune response in HIV-1-exposed uninfected neonates born from seropositive pregnant women
title Avaliação da resposta imune de neonatos não infectados pelo HIV-1 nascidos de gestantes soropositivas
spellingShingle Avaliação da resposta imune de neonatos não infectados pelo HIV-1 nascidos de gestantes soropositivas
Machado, Joana Hygino da Silva
HIV-1
AIDS
Neonates
Anti-retroviral
Lymphoproliferation
Cytokine
HIV-1
Aids
Neonatos
Anti-retroviral
Linfoproliferação
Citocinas
HIV-1
HIV (Vírus)
Infecções por HIV
AIDS (Doença)
Agentes antirretrovirais
Citocinas
CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA
title_short Avaliação da resposta imune de neonatos não infectados pelo HIV-1 nascidos de gestantes soropositivas
title_full Avaliação da resposta imune de neonatos não infectados pelo HIV-1 nascidos de gestantes soropositivas
title_fullStr Avaliação da resposta imune de neonatos não infectados pelo HIV-1 nascidos de gestantes soropositivas
title_full_unstemmed Avaliação da resposta imune de neonatos não infectados pelo HIV-1 nascidos de gestantes soropositivas
title_sort Avaliação da resposta imune de neonatos não infectados pelo HIV-1 nascidos de gestantes soropositivas
author Machado, Joana Hygino da Silva
author_facet Machado, Joana Hygino da Silva
author_role author
dc.contributor.advisor1.fl_str_mv Andrade, Arnaldo Feitosa Braga de
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/7193213149282123
dc.contributor.advisor-co1.fl_str_mv Bento, Cleonice Alves de Melo
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/6829909822082760
dc.contributor.referee1.fl_str_mv Milagres, Lucimar Gonçalves
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/0636353193914166
dc.contributor.referee2.fl_str_mv Costilla, Landi Veivi Guillermo
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/4761718254591930
dc.contributor.referee3.fl_str_mv Maximiano, Elisabeth Santos
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/5489217243902505
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/0223224432356842
dc.contributor.author.fl_str_mv Machado, Joana Hygino da Silva
contributor_str_mv Andrade, Arnaldo Feitosa Braga de
Bento, Cleonice Alves de Melo
Milagres, Lucimar Gonçalves
Costilla, Landi Veivi Guillermo
Maximiano, Elisabeth Santos
dc.subject.eng.fl_str_mv HIV-1
AIDS
Neonates
Anti-retroviral
Lymphoproliferation
Cytokine
topic HIV-1
AIDS
Neonates
Anti-retroviral
Lymphoproliferation
Cytokine
HIV-1
Aids
Neonatos
Anti-retroviral
Linfoproliferação
Citocinas
HIV-1
HIV (Vírus)
Infecções por HIV
AIDS (Doença)
Agentes antirretrovirais
Citocinas
CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA
dc.subject.por.fl_str_mv HIV-1
Aids
Neonatos
Anti-retroviral
Linfoproliferação
Citocinas
HIV-1
HIV (Vírus)
Infecções por HIV
AIDS (Doença)
Agentes antirretrovirais
Citocinas
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA
description The acquired immunodeficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV), is one the most destructive epidemic in the world, and the HIV-infection in young women has been increasing fast in the recent times. This fact has an important impact on vertical virus transmission. Although the great majority of the pediatric AIDS cases all over the world results from vertical transmission, approximately two thirds of the children exposed to the HIV during the fetal life are not infected by the virus. Many works suggest that during pregnancy, maternal infectious diseases could have complex consequences to the fetus development, and few works have explored the impact of HIV exposition on immunological responsiveness of uninfected children to different stimuli, particularly in the era of the anti-retroviral drugs. Therefore, this work aimed to evaluate immune events in HIV-1-exposed uninfected neonates born from pregnant women who controlled (G1) or not (G2) the plasma viral load, using unexposed neonates as control. Cord blood from each neonate was collected, plasma and mononuclear cells were separated and the lymphoproliferation and cytokine pattern were evaluated. The results demonstrated that the in vitro lymphoproliferation induced by polyclonal activators was higher in the G2 neonates. Nevertheless, no cell culture responded to poll synthetic HIV-1 envelope peptides. The cytokine dosage in the plasma and supernatants of polyclonally-activated cultures demonstrated that, while IL-4 and IL-10 were the dominant cytokines produced in G1 and control groups, the secretion of IFN-γ, IL-1, Il-6, IL-17 and TNF-α was significantly higher in G2 neonates. Systemic levels of IL-10 observed among the G1 neonates were higher in those born from mothers treated with viral transcriptase reverse inhibitors drugs. On the other hand, higher levels of inflammatory cytokines were observed among them born from pregnant women treated with highly active anti-retroviral therapy. In summary, our results indicate an altered immune responsiveness in neonates exposed in utero to HIV and support the role of maternal anti-viral treatment with less potent drugs to attenuate it.
publishDate 2009
dc.date.issued.fl_str_mv 2009-08-07
dc.date.available.fl_str_mv 2015-02-12
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dc.publisher.department.fl_str_mv Centro Biomédico::Faculdade de Ciências Médicas
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