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- Title
Zika Induces Human Placental Damage and Inflammation.
- Authors
Rabelo, Kíssila; de Souza, Luiz José; Salomão, Natália Gedeão; Machado, Lara Nascentes; Pereira, Priscila Gomes; Portari, Elyzabeth Avvad; Basílio-de-Oliveira, Rodrigo; dos Santos, Flávia Barreto; Neves, Laura Dias; Morgade, Luciana Faes; Provance, David William; Higa, Luiza Mendonça; Tanuri, Amilcar; de Carvalho, Jorge José; Paes, Marciano Viana
- Abstract
In Brazil, an epidemic of Zika virus (ZIKV) infections was declared in 2015 that coincided with alarming reports of microcephaly in newborns associated with mother infection. Although the virus has placental tropism, changes in the tissue morphology and immunity of infected patients have not yet been elucidated. Here, we investigated the histopathological and ultrastructural changes along with the immunological profile and the BDNF expression in rare placental material. Tissues were obtained in the 2015–2016 Brazilian epidemic, of ten ZIKV-infected patients during pregnancy, five resulting in cases of fetal microcephaly and five non-microcephaly, compared to five non-infected control placentae. Viral antigens were only detected in samples from the ZIKV infected patients. Infected placentae presented histopathological severe damage, while the ultrastructural evaluation showed abnormal organelles, such as clusters of virus-like particles consistent with the ZIKV dimensions. Increased infiltration of CD68+ and TCD8+ cells, expression of MMPs, cytokines (IFN-γ and TNF-α) and other immunological mediators (RANTES/CCL5 and VEGFR-2) confirmed excessive inflammation and vascular permeability dysfunction. An evaluation of BDNF showed a decrease that could modulate neuronal damage in the developing fetus. The placental changes caused by ZIKV are not pathognomonic, however, the data provide evidence that this infection leads to severe placental injury. Schematic drawing of placental cells detected infected with ZIKV and cytokines and mediators produced by the mononuclear inflammatory infiltrate. The scheme represents the functional unit of the placenta (chorionic villus) and the maternal region (decidua), comprised of cytotrophoblast (CTB), endothelial cells (En), syncytiotrophoblast (STB), mesenchymal cells (MS), fibroblasts (Fi), Hofbauer (Hf), macrophages (MØ), decidual cells (DC), and extracellular matrix, containing collagen (COL). In the placentae of infected patients, ZIKV antigens were detected in all these cells and there was an increase in the number of macrophages and Hofbauer cells, which are responsible for the production of matrix metalloproteinases that degrade the collagen as well as TNF-α that activates and attracts other immune cells. There was also an increase in T CD8+ lymphocytes, responsible for the production of IFN-γ, which further activates macrophages. In endothelial cells, there was large expression of VEGFR-2 and RANTES, which increases vascular permeability and are able to induce macrophages migration.
- Subjects
BRAZIL; CHORIONIC villi; VIRAL antigens; MATRIX metalloproteinases; EXTRACELLULAR matrix; CLUSTERING of particles; ABRUPTIO placentae
- Publication
Frontiers in Immunology, 2020, Vol 11, pN.PAG
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2020.02146