The role of complement and neutrophils at the cervico-vaginal interface in microbial-driven preterm birth
Author(s)
Gimeno Molina, Belen
Type
Thesis
Abstract
Preterm birth (PTB) is a syndrome with many underlying aetiologies that occurs in 10% of pregnancies, and affects approximately 15 million newborns each year. There are clear associations between vaginal microbial composition and the risk of cervical shortening and preterm birth. Lactobacillus crispatus dominance is protective and associated with uncomplicated pregnancies, whereas L. iners and high diversity communities confer a higher risk. However, the mechanisms driving microbial-host immune interactions and PTB remain poorly understood.
This PhD has investigated how the innate and adaptive immune responses at the cervicovaginal interface contribute to microbial-driven cervical shortening and preterm birth. To do so, three specific aims were established: 1) to determine if the complement system modulates the risk of spontaneous preterm birth in women who have a high-risk microbial signature; 2) to determine if the immunophenotype of cervical neutrophils influences the local immune milieu in response to a high-risk microbial signature, cervical shortening and preterm labour; and 3) to determine if the recognition of vaginal microbiota by opsonins differs by microbial composition, and in cases of cervical shortening and preterm birth.
This thesis reports on an increase in cytokines and complement proteins in association with the local cervicovaginal microbial composition, cervical shortening and preterm birth. It was found that cervical neutrophils were more activated than peripheral neutrophils and that their immunophenotype correlated with vaginal microbial composition and increased concentrations of cytokines and complement proteins.
Cervicovaginal microbial composition differed in opsonisation status as determined by flow cytometry, with higher percentages of opsonisation in women with L. crispatus vaginal dominance. This was associated with lower concentrations of complement proteins and term birth, suggesting a potential role for opsonins in vaginal homeostasis during pregnancy...
This PhD has investigated how the innate and adaptive immune responses at the cervicovaginal interface contribute to microbial-driven cervical shortening and preterm birth. To do so, three specific aims were established: 1) to determine if the complement system modulates the risk of spontaneous preterm birth in women who have a high-risk microbial signature; 2) to determine if the immunophenotype of cervical neutrophils influences the local immune milieu in response to a high-risk microbial signature, cervical shortening and preterm labour; and 3) to determine if the recognition of vaginal microbiota by opsonins differs by microbial composition, and in cases of cervical shortening and preterm birth.
This thesis reports on an increase in cytokines and complement proteins in association with the local cervicovaginal microbial composition, cervical shortening and preterm birth. It was found that cervical neutrophils were more activated than peripheral neutrophils and that their immunophenotype correlated with vaginal microbial composition and increased concentrations of cytokines and complement proteins.
Cervicovaginal microbial composition differed in opsonisation status as determined by flow cytometry, with higher percentages of opsonisation in women with L. crispatus vaginal dominance. This was associated with lower concentrations of complement proteins and term birth, suggesting a potential role for opsonins in vaginal homeostasis during pregnancy...
Version
Open Access
Date Issued
2023-02-14
Date Awarded
2023-07-01
Copyright Statement
Attribution-NonCommercial 4.0 International Licence (CC BY-NC)
License URL
Advisor
Sykes, Lynne
Kropf, Pascale
MacIntyre, David
Bennett, Phillip
Sponsor
March of Dimes (Charity)
Publisher Department
Department of Metabolism, Digestion and Reproduction
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)