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Neutrophils Dominate the Cervical Immune Cell Population in Pregnancy and Their Transcriptome Correlates With the Microbial Vaginal Environment

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Amirah Mohd Zaki, Alicia Hadingham, Flavia Flaviani, Yasmin Haque, Jia Dai Mi, Debbie Finucane, Giorgia Dalla Valle, A. James Mason, Mansoor Saqi, Deena L. Gibbons, Rachel M. Tribe

Original languageEnglish
Article number904451
JournalFrontiers in microbiology
Volume13
DOIs
Published14 Jun 2022

Bibliographical note

Funding Information: AH (Doctoral fellowship), AZ, FF, and MS are all funded by the NIHR Biomedical Research Centre (BRC) based at Guy’s and St. Thomas’ National Health Service Foundation Trust. Funding for the INSIGHT cohort that provided samples and data for this study was provided from Tommy’s Charity (Reg charity no. 1060508); NIHR Biomedical Research Centre (BRC) based at Guy’s and St. Thomas’ National Health Service Foundation Trust, the Rosetrees Trust (no. 298582, M303-CD1), Borne Foundation (no. 1167073) and Action Medical Research grant held by DG (GN2790). Funding Information: The authors acknowledge use of the research computing facility at King’s College London, Rosalind (https://rosalind.kcl.ac.uk), which is delivered in partnership with the National Institute for Health Research (NIHR) Biomedical Research Centres at South London & Maudsley and Guy’s & St. Thomas’ NHS Foundation Trusts, and part-funded by capital equipment grants from the Maudsley Charity (award 980) and Guy’s & St. Thomas’ Charity (TR130505). We thank the Women and Children’s Health CRN and biobank teams, and all participants. Funding Information: The authors acknowledge use of the research computing facility at King’s College London, Rosalind ( https://rosalind.kcl.ac.uk ), which is delivered in partnership with the National Institute for Health Research (NIHR) Biomedical Research Centres at South London & Maudsley and Guy’s & St. Thomas’ NHS Foundation Trusts, and part-funded by capital equipment grants from the Maudsley Charity (award 980) and Guy’s & St. Thomas’ Charity (TR130505). We thank the Women and Children’s Health CRN and biobank teams, and all participants. Publisher Copyright: Copyright © 2022 Mohd Zaki, Hadingham, Flaviani, Haque, Mi, Finucane, Dalla Valle, Mason, Saqi, Gibbons and Tribe.

King's Authors

Abstract

The cervicovaginal environment in pregnancy is proposed to influence risk of spontaneous preterm birth. The environment is shaped both by the resident microbiota and local inflammation driven by the host response (epithelia, immune cells and mucous). The contributions of the microbiota, metabolome and host defence peptides have been investigated, but less is known about the immune cell populations and how they may respond to the vaginal environment. Here we investigated the maternal immune cell populations at the cervicovaginal interface in early to mid-pregnancy (10–24 weeks of gestation, samples from N = 46 women), we confirmed neutrophils as the predominant cell type and characterised associations between the cervical neutrophil transcriptome and the cervicovaginal metagenome (N = 9 women). In this exploratory study, the neutrophil cell proportion was affected by gestation at sampling but not by birth outcome or ethnicity. Following RNA sequencing (RNA-seq) of a subset of neutrophil enriched cells, principal component analysis of the transcriptome profiles indicated that cells from seven women clustered closely together these women had a less diverse cervicovaginal microbiota than the remaining three women. Expression of genes involved in neutrophil mediated immunity, activation, degranulation, and other immune functions correlated negatively with Gardnerella vaginalis abundance and positively with Lactobacillus iners abundance; microbes previously associated with birth outcome. The finding that neutrophils are the dominant immune cell type in the cervix during pregnancy and that the cervical neutrophil transcriptome of pregnant women may be modified in response to the microbial cervicovaginal environment, or vice versa, establishes the rationale for investigating associations between the innate immune response, cervical shortening and spontaneous preterm birth and the underlying mechanisms.

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