Omega-3 fatty acids suppress Fusobacterium nucleatum-induced placental inflammation originating from maternal endothelial cells

Fusobacterium nucleatum is an oral anaerobe prevalent in intrauterine infection associated with a wide spectrum of adverse pregnancy outcomes. We demonstrate here that F. nucleatum triggers placental inflammation through maternal, rather than paternal, TLR4-mediated signaling. Elimination of TLR4 from maternal endothelial cells alleviated placental inflammation and reduced fetal and neonatal death, while elimination of TLR4 in the hematopoietic cells had no effect. The placental inflammatory response followed a spatiotemporal pattern, with NF-κB activation observed first in the maternal endothelial cells and then in the decidual cells surrounding the endothelium, followed by induction of inflammatory cytokines and chemokines. Supplementation of pregnant mice with fish oil as a source of omega-3 fatty acids suppressed placental inflammation, reduced F. nucleatum proliferation in the placenta, and increased fetal and neonatal survival. In vitro analysis illustrates that omega-3 fatty acids inhibit bacterial-induced inflammatory responses from human umbilical cord endothelial cells. Our study therefore reveals a mechanism by which microbial infections affect pregnancy and identifies a prophylactic therapy to protect against intrauterine infections.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:4

Enthalten in:

JCI insight - 4(2019), 3 vom: 07. Feb.

Sprache:

Englisch

Beteiligte Personen:

Garcia-So, Jeewon [VerfasserIn]
Zhang, Xinwen [VerfasserIn]
Yang, Xiaohua [VerfasserIn]
Rubinstein, Mara Roxana [VerfasserIn]
Mao, De Yu [VerfasserIn]
Kitajewski, Jan [VerfasserIn]
Liu, Kang [VerfasserIn]
Han, Yiping W [VerfasserIn]

Links:

Volltext

Themen:

Bacterial infections
Journal Article
Microbiology

Anmerkungen:

Date Revised 12.04.2024

published: Electronic

Citation Status PubMed-not-MEDLINE

doi:

10.1172/jci.insight.125436

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM293544328