TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria

Abstract 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 (...

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Autores principales:	Renato Barboza, Flávia Afonso Lima, Aramys Silva Reis, Oscar Javier Murillo, Erika Paula Machado Peixoto, Carla Letícia Bandeira, Wesley Luzetti Fotoran, Luis Roberto Sardinha, Gerhard Wunderlich, Estela Bevilacqua, Maria Regina D’Império Lima, José Maria Alvarez, Fabio Trindade Maranhão Costa, Lígia Antunes Gonçalves, Sabrina Epiphanio, Claudio Romero Farias Marinho
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/50608ad8eaf04672a8ab0ac58a586af4
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spelling	oai:doaj.org-article:50608ad8eaf04672a8ab0ac58a586af42021-12-02T15:05:39ZTLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria10.1038/s41598-017-08299-x2045-2322https://doaj.org/article/50608ad8eaf04672a8ab0ac58a586af42017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08299-xhttps://doaj.org/toc/2045-2322Abstract 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 NK65GFP 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.Renato BarbozaFlávia Afonso LimaAramys Silva ReisOscar Javier MurilloErika Paula Machado PeixotoCarla Letícia BandeiraWesley Luzetti FotoranLuis Roberto SardinhaGerhard WunderlichEstela BevilacquaMaria Regina D’Império LimaJosé Maria AlvarezFabio Trindade Maranhão CostaLígia Antunes GonçalvesSabrina EpiphanioClaudio Romero Farias MarinhoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Renato Barboza Flávia Afonso Lima Aramys Silva Reis Oscar Javier Murillo Erika Paula Machado Peixoto Carla Letícia Bandeira Wesley Luzetti Fotoran Luis Roberto Sardinha Gerhard Wunderlich Estela Bevilacqua Maria Regina D’Império Lima José Maria Alvarez Fabio Trindade Maranhão Costa Lígia Antunes Gonçalves Sabrina Epiphanio Claudio Romero Farias Marinho TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria
description	Abstract 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 NK65GFP 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.
format	article
author	Renato Barboza Flávia Afonso Lima Aramys Silva Reis Oscar Javier Murillo Erika Paula Machado Peixoto Carla Letícia Bandeira Wesley Luzetti Fotoran Luis Roberto Sardinha Gerhard Wunderlich Estela Bevilacqua Maria Regina D’Império Lima José Maria Alvarez Fabio Trindade Maranhão Costa Lígia Antunes Gonçalves Sabrina Epiphanio Claudio Romero Farias Marinho
author_facet	Renato Barboza Flávia Afonso Lima Aramys Silva Reis Oscar Javier Murillo Erika Paula Machado Peixoto Carla Letícia Bandeira Wesley Luzetti Fotoran Luis Roberto Sardinha Gerhard Wunderlich Estela Bevilacqua Maria Regina D’Império Lima José Maria Alvarez Fabio Trindade Maranhão Costa Lígia Antunes Gonçalves Sabrina Epiphanio Claudio Romero Farias Marinho
author_sort	Renato Barboza
title	TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria
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
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/50608ad8eaf04672a8ab0ac58a586af4
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TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria

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