دورية أكاديمية
TLR4-Endothelin Axis Controls Syncytiotrophoblast Motility and Confers Fetal Protection in Placental Malaria.
| العنوان: | TLR4-Endothelin Axis Controls Syncytiotrophoblast Motility and Confers Fetal Protection in Placental Malaria. |
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| المؤلفون: | Pandya Y; Instituto Gulbenkian de Ciência, Oeiras, Portugal., Marta A; Instituto Gulbenkian de Ciência, Oeiras, Portugal., Barateiro A; Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Prof. Lineu Prestes, São Paulo, São Paulo, Brazil., Bandeira CL; Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Prof. Lineu Prestes, São Paulo, São Paulo, Brazil., Dombrowski JG; Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Prof. Lineu Prestes, São Paulo, São Paulo, Brazil., Costa J; Instituto Gulbenkian de Ciência, Oeiras, Portugal., Marinho CRF; Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Prof. Lineu Prestes, São Paulo, São Paulo, Brazil., Penha-Gonçalves C; Instituto Gulbenkian de Ciência, Oeiras, Portugal. |
| المصدر: | Infection and immunity [Infect Immun] 2021 Jul 15; Vol. 89 (8), pp. e0080920. Date of Electronic Publication: 2021 Jul 15. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0246127 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-5522 (Electronic) Linking ISSN: 00199567 NLM ISO Abbreviation: Infect Immun Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington, DC : American Society For Microbiology Original Publication: [Bethesda, Md.] American Society for Microbiology. |
| مواضيع طبية MeSH: | Signal Transduction*, Endothelins/*metabolism , Placenta/*metabolism , Placenta/*parasitology , Toll-Like Receptor 4/*metabolism , Trophoblasts/*metabolism, Biomarkers ; Brazil ; Female ; Host-Pathogen Interactions/immunology ; Humans ; Malaria/immunology ; Malaria/metabolism ; Malaria/parasitology ; Placenta/immunology ; Pregnancy ; Pregnancy Complications, Parasitic ; Pregnancy Outcome |
| مستخلص: | 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 Toll-like receptor 4 (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 abrogates 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. |
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| معلومات مُعتمدة: | Z01 AI000809 United States ImNIH Intramural NIH HHS |
| فهرسة مساهمة: | Keywords: Toll-like receptor 4; endothelin; endothelin receptor B; placental malaria; trophoblasts |
| المشرفين على المادة: | 0 (Biomarkers) 0 (Endothelins) 0 (TLR4 protein, human) 0 (Toll-Like Receptor 4) |
| تواريخ الأحداث: | Date Created: 20210601 Date Completed: 20210920 Latest Revision: 20220116 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC8281214 |
| DOI: | 10.1128/IAI.00809-20 |
| PMID: | 34061587 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1098-5522 |
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| DOI: | 10.1128/IAI.00809-20 |