TLR4-endothelin axis controls syncytiotrophoblast motility and confers fetal protection in placental malaria

Pregnancy associated malaria is often associated with adverse pregnancy outcomes. Placental circulatory impairments are an intriguing and unsolved component of malaria pathophysiology. Here, we uncovered a TLR4-TRIF-endothelin axis that controls trophoblast motility and is linked to fetal protection during Plasmodium infection. In a cohort of 401 pregnancies from Northern Brazil we found that infection during pregnancy reduced expression of endothelin receptor B in syncytiotrophoblasts while endothelin expression was only affected during acute infection. We further show that quantitative expression of placental endothelin and endothelin receptor B proteins are differentially controlled by maternal and fetal TLR4 alleles. Using murine malaria models, we identified placental autonomous responses to malaria infection mediated by fetally encoded TLR4 that not only controlled placental endothelin gene expression but also correlated with fetal viability protection. In vitro assays showed that control of endothelin expression in fetal syncytiotrophoblasts exposed to Plasmodium -infected erythrocytes was dependent on TLR4 via the TRIF pathway but not MyD88 signaling. Time-lapse microscopy in syncytiotrophoblast primary cultures and cell invasion assays demonstrated that ablation of TLR4 or endothelin receptor blockade abrogate trophoblast collective motility and cell migration responses to infected erythrocytes. These results cohesively substantiate the hypothesis that fetal innate immune sensing, namely the TRL4-TRIF pathway exerts a fetal protective role during malaria infection by mediating syncytiotrophoblast vasoregulatory responses that counteract placental insufficiency.

Effects of polymorphisms in the endothelin receptor B subtype 2 gene on plumage colour in mule ducks

The aim of the present study was to investigate the effect of a single nucleotide polymorphism (SNP) of the endothelin receptor B subtype 2 (EDNRB2) gene on plumage coloration in mule ducks. Test mating (white Tsaiya × white Muscovy ducks) in combination with polymerase chain reaction restriction fragment length polymorphism (PCR RFLP) was performed to investigate the effect of non synonymous SNPs in two maternal lines (a conservation and a selection population) on plumage coloration in mule ducks. One non synonymous SNP (c.995G>A) was identified in white Muscovy ducks and white Tsaiya ducks by PCR high resolution melting (PCR HRM) and DNA sequencing. Genotyping results showed that the c.995G>A locus is associated with plumage colour in two maternal populations of white Tsaiya ducks. Further, the maternal genotype of c.995G>A SNP affects the plumage colour of mule ducks. Therefore, the polymorphisms within the EDNRB2 gene at c.995G>A in white Tsaiya ducks may be used in marker assisted selection to improve the plumage colour of mule ducks. Keywords: Muscovy drakes, polymerase chain reaction restriction fragment length, single nucleotide polymorphism, Tsaiya ducks