Neutrophil infiltration leads to fetal growth restriction by impairing the placental vasculature in DENV-infected pregnant mice.
Adverse pregnancy outcomes
Dengue virus
Matrix metalloproteinase
Neutrophil
Placenta
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
09
11
2022
revised:
22
06
2023
accepted:
18
07
2023
medline:
18
9
2023
pubmed:
7
8
2023
entrez:
6
8
2023
Statut:
ppublish
Résumé
Dengue virus (DENV) infection during pregnancy increases the risk of adverse fetal outcomes, which has become a new clinical challenge. However, the underlying mechanism remains unknown. The effect of DENV-2 infection on fetuses was investigated using pregnant interferon α/β receptor-deficient (Ifnar1 Fetal growth restriction observed in DENV-2 infection was mainly caused by the destruction of the placental vasculature rather than direct damage from the virus in our mouse model. After infection, neutrophil infiltration into the placenta disrupts the expression profile of matrix metalloproteinases, which leads to placental dysvascularization and insufficiency. Notably, similar histopathological changes were observed in the placentas from DENV-infected puerperae. Neutrophils play key roles in placental histopathological damage during DENV infection, which indicates that interfering with aberrant neutrophil infiltration into the placenta may be an important therapeutic target for adverse pregnancy outcomes in DENV infection. The National Key Research and Development Plans of China (2021YFC2300200-02 to J.A., 2019YFC0121905 to Q.Z.C.), the National Natural Science Foundation of China (NSFC) (U1902210 and 81972979 to J. A., 81902048 to Z. Y. S., and 82172266 to P.G.W.), and the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan, China (IDHT20190510 to J. A.).
Sections du résumé
BACKGROUND
BACKGROUND
Dengue virus (DENV) infection during pregnancy increases the risk of adverse fetal outcomes, which has become a new clinical challenge. However, the underlying mechanism remains unknown.
METHODS
METHODS
The effect of DENV-2 infection on fetuses was investigated using pregnant interferon α/β receptor-deficient (Ifnar1
FINDINGS
RESULTS
Fetal growth restriction observed in DENV-2 infection was mainly caused by the destruction of the placental vasculature rather than direct damage from the virus in our mouse model. After infection, neutrophil infiltration into the placenta disrupts the expression profile of matrix metalloproteinases, which leads to placental dysvascularization and insufficiency. Notably, similar histopathological changes were observed in the placentas from DENV-infected puerperae.
INTERPRETATION
CONCLUSIONS
Neutrophils play key roles in placental histopathological damage during DENV infection, which indicates that interfering with aberrant neutrophil infiltration into the placenta may be an important therapeutic target for adverse pregnancy outcomes in DENV infection.
FUNDING
BACKGROUND
The National Key Research and Development Plans of China (2021YFC2300200-02 to J.A., 2019YFC0121905 to Q.Z.C.), the National Natural Science Foundation of China (NSFC) (U1902210 and 81972979 to J. A., 81902048 to Z. Y. S., and 82172266 to P.G.W.), and the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan, China (IDHT20190510 to J. A.).
Identifiants
pubmed: 37544202
pii: S2352-3964(23)00304-3
doi: 10.1016/j.ebiom.2023.104739
pmc: PMC10432184
pii:
doi:
Substances chimiques
Cytokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
104739Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted.