TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/51385 http://dx.doi.org/10.1038/s41598-017-08299-x |
Resumo: | Malaria-associate pregnancy has a significant impact on infant morbidity and mortality. The detrimental effects of malaria infection during pregnancy have been shown to correlate with immune activation in the placental tissue. Herein we sought to evaluate the effect of Toll-like receptors (TLRs) activation on placental malaria (PM) development by using the Plasmodium berghei NK65(GFP) infection model. We observed that activation of the innate immune system by parasites leads to PM due to local inflammation. We identified TLR4 activation as the main pathway involved in the inflammatory process in the placental tissue since the absence of functional TLR4 in mice leads to a decrease in the pro-inflammatory responses, which resulted in an improved pregnancy outcome. Additionally, a similar result was obtained when infected pregnant mice were treated with IAXO-101, a TLR4/CD14 blocker. Together, this study illustrates the importance of TLR4 signalling for the generation of the severe inflammatory response involved in PM pathogenesis. Therefore, our results implicate that TLR4 blockage could be a potential candidate for therapeutic interventions to reduce malaria-induced pathology both in the mother and the fetus. |
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Barboza, Renato [UNIFESP]Lima, Flavia AfonsoReis, Aramys SilvaMurillo, Oscar JavierMachado Peixoto, Erika PaulaBandeira, Carla LeticiaFotoran, Wesley LuzettiSardinha, Luis RobertoWunderlich, GerhardBevilacqua, EstelaD'Imperio Lima, Maria ReginaAlvarez, Jose MariaMaranhao Costa, Fabio TrindadeGoncalves, Ligia AntunesEpiphanio, SabrinaFarias Marinho, Cludio Romerso2019-08-19T11:49:43Z2019-08-19T11:49:43Z2017Scientific Reports. London, v. 7, p. -, 2017.2045-2322http://repositorio.unifesp.br/handle/11600/51385http://dx.doi.org/10.1038/s41598-017-08299-xWOS000407864400004.pdf10.1038/s41598-017-08299-xWOS:000407864400004Malaria-associate pregnancy has a significant impact on infant morbidity and mortality. The detrimental effects of malaria infection during pregnancy have been shown to correlate with immune activation in the placental tissue. Herein we sought to evaluate the effect of Toll-like receptors (TLRs) activation on placental malaria (PM) development by using the Plasmodium berghei NK65(GFP) infection model. We observed that activation of the innate immune system by parasites leads to PM due to local inflammation. We identified TLR4 activation as the main pathway involved in the inflammatory process in the placental tissue since the absence of functional TLR4 in mice leads to a decrease in the pro-inflammatory responses, which resulted in an improved pregnancy outcome. Additionally, a similar result was obtained when infected pregnant mice were treated with IAXO-101, a TLR4/CD14 blocker. Together, this study illustrates the importance of TLR4 signalling for the generation of the severe inflammatory response involved in PM pathogenesis. Therefore, our results implicate that TLR4 blockage could be a potential candidate for therapeutic interventions to reduce malaria-induced pathology both in the mother and the fetus.Fundação de Amparo a Pesquisa do Estado de São Paulo - FAPESPCoordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESConselho Nacional de Desenvolvimento Científico e Tecnológico - CNPqUniv Fed São Paulo, Dept Ciencias Biol, Diadema, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Parasitol, São Paulo, BrazilHosp Israelita Albert Einstein, São Paulo, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Biol Celular & Desenvolvimento, São Paulo, BrazilUniv Estadual Campinas, Dept Genet Evolucao & Bioagentes, Inst Biol, Campinas, SP, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Imunol, São Paulo, BrazilUniv São Paulo, Dept Analises Clin & Toxicol, Fac Ciencias Farmaceut, São Paulo, BrazilUniv Fed São Paulo, Dept Ciencias Biol, Diadema, BrazilFAPESP: 2009/53889-0FAPESP: 2014/09964-5FAPESP: 2014/20451-0FAPESP: 2012/16525-2FAPESP: 2011/17880-8FAPESP: 2013/16417-8FAPESP: 2011/19048-8FAPESP: 2013/00981-1FAPESP: 2015/06106-0]CAPES: AUX-PE-PNPD 2751/2010CNPq: 475771/2009-5Web of Science-engNature Publishing GroupTLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malariainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000407864400004.pdfapplication/pdf10532894${dspace.ui.url}/bitstream/11600/51385/1/WOS000407864400004.pdf04bfa25993020f0b28870c6493e4c0adMD51open accessTEXTWOS000407864400004.pdf.txtWOS000407864400004.pdf.txtExtracted texttext/plain51824${dspace.ui.url}/bitstream/11600/51385/8/WOS000407864400004.pdf.txt36bc4de4e295ae809ce126c23aa83ca9MD58open accessTHUMBNAILWOS000407864400004.pdf.jpgWOS000407864400004.pdf.jpgIM Thumbnailimage/jpeg7565${dspace.ui.url}/bitstream/11600/51385/10/WOS000407864400004.pdf.jpg55eb1cf00e348a29be4eb4370e0e46a2MD510open access11600/513852023-06-05 19:28:48.308open accessoai:repositorio.unifesp.br:11600/51385Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-06-05T22:28:48Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria |
title |
TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria |
spellingShingle |
TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria Barboza, Renato [UNIFESP] |
title_short |
TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria |
title_full |
TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria |
title_fullStr |
TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria |
title_full_unstemmed |
TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria |
title_sort |
TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria |
author |
Barboza, Renato [UNIFESP] |
author_facet |
Barboza, Renato [UNIFESP] Lima, Flavia Afonso Reis, Aramys Silva Murillo, Oscar Javier Machado Peixoto, Erika Paula Bandeira, Carla Leticia Fotoran, Wesley Luzetti Sardinha, Luis Roberto Wunderlich, Gerhard Bevilacqua, Estela D'Imperio Lima, Maria Regina Alvarez, Jose Maria Maranhao Costa, Fabio Trindade Goncalves, Ligia Antunes Epiphanio, Sabrina Farias Marinho, Cludio Romerso |
author_role |
author |
author2 |
Lima, Flavia Afonso Reis, Aramys Silva Murillo, Oscar Javier Machado Peixoto, Erika Paula Bandeira, Carla Leticia Fotoran, Wesley Luzetti Sardinha, Luis Roberto Wunderlich, Gerhard Bevilacqua, Estela D'Imperio Lima, Maria Regina Alvarez, Jose Maria Maranhao Costa, Fabio Trindade Goncalves, Ligia Antunes Epiphanio, Sabrina Farias Marinho, Cludio Romerso |
author2_role |
author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Barboza, Renato [UNIFESP] Lima, Flavia Afonso Reis, Aramys Silva Murillo, Oscar Javier Machado Peixoto, Erika Paula Bandeira, Carla Leticia Fotoran, Wesley Luzetti Sardinha, Luis Roberto Wunderlich, Gerhard Bevilacqua, Estela D'Imperio Lima, Maria Regina Alvarez, Jose Maria Maranhao Costa, Fabio Trindade Goncalves, Ligia Antunes Epiphanio, Sabrina Farias Marinho, Cludio Romerso |
description |
Malaria-associate pregnancy has a significant impact on infant morbidity and mortality. The detrimental effects of malaria infection during pregnancy have been shown to correlate with immune activation in the placental tissue. Herein we sought to evaluate the effect of Toll-like receptors (TLRs) activation on placental malaria (PM) development by using the Plasmodium berghei NK65(GFP) infection model. We observed that activation of the innate immune system by parasites leads to PM due to local inflammation. We identified TLR4 activation as the main pathway involved in the inflammatory process in the placental tissue since the absence of functional TLR4 in mice leads to a decrease in the pro-inflammatory responses, which resulted in an improved pregnancy outcome. Additionally, a similar result was obtained when infected pregnant mice were treated with IAXO-101, a TLR4/CD14 blocker. Together, this study illustrates the importance of TLR4 signalling for the generation of the severe inflammatory response involved in PM pathogenesis. Therefore, our results implicate that TLR4 blockage could be a potential candidate for therapeutic interventions to reduce malaria-induced pathology both in the mother and the fetus. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017 |
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2019-08-19T11:49:43Z |
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2019-08-19T11:49:43Z |
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article |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
Scientific Reports. London, v. 7, p. -, 2017. |
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http://repositorio.unifesp.br/handle/11600/51385 http://dx.doi.org/10.1038/s41598-017-08299-x |
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2045-2322 |
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WOS000407864400004.pdf |
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10.1038/s41598-017-08299-x |
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WOS:000407864400004 |
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Scientific Reports. London, v. 7, p. -, 2017. 2045-2322 WOS000407864400004.pdf 10.1038/s41598-017-08299-x WOS:000407864400004 |
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