Complement and neutrophils are actively involved at the cervicovaginal interface in cases of adverse microbial composition, cervical shortening and spontaneous preterm birth
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Microbial-driven spontaneous preterm birth (sPTB) is linked to adverse vaginal microbiome and dysregulated immune responses, yet this knowledge has not translated into predictive tools or therapies. We sampled 186 high-risk pregnant women and assessed 14 complement proteins and the neutrophil immunophenotype at the cervicovaginal interface to expand potential targets. Alterations in classical and alternative complement pathway components were associated with bacterial community composition and preceded cervical shortening and sPTB. At 12⁺⁰–16⁺⁶ weeks, women with Community State Type (CST) IV had significantly higher concentrations of C1q, C4, C4b, Factor B,D, C3b/iC3b, and Factor H,I than those with CST I. Women who later developed a short cervix and delivered preterm showed lower L. crispatus abundance and elevated complement activation. Neutrophils were the dominant local immune cell and exhibited enhanced activation relative to peripheral neutrophils, with altered expression of CD11b, CD62L, CD63, and CD66b. Cervical neutrophil CD63, CD66b, and CD88 differed between CST IV and CST I, though not by pregnancy outcome. Neutrophil abundance correlated with cytokines, complement proteins, and MMPs, suggesting roles in inflammation and tissue remodelling. These findings highlight a microbiota-driven complement–neutrophil axis present before cervical remodelling and sPTB, identifying potential complement-based predictors and therapeutic targets.
Date Issued
2026-08-10
Date Acceptance
2026-03-11
Citation
npj Biofilms and Microbiomes, 2026, 12
ISSN
2055-5008
Publisher
Nature Portfolio
Journal / Book Title
npj Biofilms and Microbiomes
Volume
12
Copyright Statement
© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ .
License URL
Identifier
10.1038/s41522-026-00969-x
Subjects
cervical shortening
complement proteins
cytokines
neutrophils
vaginal microbiome
immune modulation
Publication Status
Published
Article Number
ARTN 152
Date Publish Online
2025-04-15