Gardnerella vaginalis induces matrix metalloproteinases in the cervicovaginal epithelium through TLR-2 activation.
Black People
Case-Control Studies
Cervix Uteri
/ metabolism
Epithelium
/ metabolism
Female
Gardnerella vaginalis
Gram-Positive Bacterial Infections
/ metabolism
Humans
Infant, Newborn
Intercellular Signaling Peptides and Proteins
/ metabolism
Lactobacillus
Matrix Metalloproteinase 9
/ metabolism
Membrane Proteins
/ metabolism
Pregnancy
Pregnancy Complications, Infectious
/ metabolism
Premature Birth
Prospective Studies
Toll-Like Receptor 2
/ metabolism
Vagina
Vaginosis, Bacterial
/ metabolism
Lactobacillus-deficient microbiota
MMP-9
Matrix metalloproteinase
Short cervix
Spontaneous preterm birth
TLR-2
Journal
Journal of reproductive immunology
ISSN: 1872-7603
Titre abrégé: J Reprod Immunol
Pays: Ireland
ID NLM: 8001906
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
04
02
2022
revised:
07
05
2022
accepted:
20
05
2022
pubmed:
10
6
2022
medline:
20
7
2022
entrez:
9
6
2022
Statut:
ppublish
Résumé
Lactobacillus-deficient cervicovaginal microbiota, including Gardnerella vaginalis, are implicated in cervical remodeling and preterm birth. Mechanisms by which microbes drives outcomes are not fully elucidated. We hypothesize that Gardnerella vaginalis induces matrix metalloproteinases through TLR-2, leading to epithelial barrier dysfunction and premature cervical remodeling. Cervicovaginal cells were treated with live Gardnerella vaginalis or Lactobacillus crispatus or their bacteria-free supernatants for 24 h. For TLR-2 experiments, cells were pretreated with TLR-2 blocking antibody. A Luminex panel was run on cell media. For human data, we conducted a case-control study from a prospective pregnancy cohort of Black individuals with spontaneous preterm (sPTB) (n = 40) or term (n = 40) births whose vaginal microbiota had already been characterized. Cervicovaginal fluid was obtained between 20 and 24 weeks' gestation. Short cervix was defined as < 25 mm by second trimester transvaginal ultrasound. MMP-9 was quantified by ELISA. Standard analytical approaches were used to determine differences across in vitro conditions, as well as MMP-9 and associations with clinical outcomes. Gardnerella vaginalis induced MMP-1 in cervical cells (p = 0.01) and MMP-9 in cervical and vaginal (VK2) cells (p ≤ 0.001 for all). TLR-2 blockade mitigated MMP-9 induction by Gardnerella vaginalis. MMP-9 in cervicovaginal fluid is higher among pregnant individuals with preterm birth, short cervix, and Lactobacillus-deficient microbiota (p < 0.05 for all). MMP-9 is increased in the cervicovaginal fluid of pregnant individuals with subsequent sPTB. Our in vitro work ascribes a potential mechanism by which a cervicovaginal microbe, commonly associated with adverse pregnancy outcomes, may disrupt the cervicovaginal epithelial barrier and promote premature cervical remodeling in spontaneous preterm birth.
Identifiants
pubmed: 35679790
pii: S0165-0378(22)00177-2
doi: 10.1016/j.jri.2022.103648
pmc: PMC9313515
mid: NIHMS1822435
pii:
doi:
Substances chimiques
Intercellular Signaling Peptides and Proteins
0
Membrane Proteins
0
Toll-Like Receptor 2
0
Tril protein, mouse
0
MMP9 protein, human
EC 3.4.24.35
Matrix Metalloproteinase 9
EC 3.4.24.35
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
103648Subventions
Organisme : NCI NIH HHS
ID : P30 CA016520
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD098867
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD102318
Pays : United States
Organisme : NINR NIH HHS
ID : R01 NR014784
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier B.V. All rights reserved.
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