TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria (vol 7, 2017)

Malaria-associate pregnancy has a signifcant impact on infant morbidity and mortality. The detrimental efects of malaria infection during pregnancy have been shown to correlate with immune activation in the placental tissue. Herein we sought to evaluate the efect 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 infammation. We identifed TLR4 activation as the main pathway involved in the infammatory process in the placental tissue since the absence of functional TLR4 in mice leads to a decrease in the pro-infammatory 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 infammatory 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.Univ Fed Sao Paulo, Dept Ciencias Biol, Diadema, BrazilUniv Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, Sao Paulo, BrazilHosp Israelita Albert Einstein, Sao Paulo, BrazilUniv Sao Paulo, Dept Biol Celular & Desenvolvimento, Sao Paulo, BrazilUniv Estadual Campinas, Inst Biol, Dept Genet Evolucao & Bioagentes, Campinas, SP, BrazilUniv Sao Paulo, Inst Ciencias Biomed, Dept Imunol, Sao Paulo, BrazilUniv Sao aulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Ciencias Biol, Diadema, BrazilWeb of Scienc