TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria

TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria

Author Barboza, Renato Autor UNIFESP Google Scholar
Lima, Flavia Afonso Google Scholar
Reis, Aramys Silva Google Scholar
Murillo, Oscar Javier Google Scholar
Machado Peixoto, Erika Paula Google Scholar
Bandeira, Carla Leticia Google Scholar
Fotoran, Wesley Luzetti Google Scholar
Sardinha, Luis Roberto Google Scholar
Wunderlich, Gerhard Google Scholar
Bevilacqua, Estela Google Scholar
D'Imperio Lima, Maria Regina Google Scholar
Alvarez, Jose Maria Google Scholar
Maranhao Costa, Fabio Trindade Google Scholar
Goncalves, Ligia Antunes Google Scholar
Epiphanio, Sabrina Google Scholar
Farias Marinho, Cludio Romerso Google Scholar
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 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.
Language English
Sponsor Fundação de Amparo a Pesquisa do Estado de São Paulo - FAPESP
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq
Grant number FAPESP: 2009/53889-0
FAPESP: 2014/09964-5
FAPESP: 2014/20451-0
FAPESP: 2012/16525-2
FAPESP: 2011/17880-8
FAPESP: 2013/16417-8
FAPESP: 2011/19048-8
FAPESP: 2013/00981-1
FAPESP: 2015/06106-0]
CAPES: AUX-PE-PNPD 2751/2010
CNPq: 475771/2009-5
Date 2017
Published in Scientific Reports. London, v. 7, p. -, 2017.
ISSN 2045-2322 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent -
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000407864400004

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