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Immune Control of Group B Streptococcal Placental

B 族链球菌胎盘的免疫控制

基本信息

批准号：
10687155
负责人：
KRISTINA M. ADAMS WALDORF
金额：
$ 88万
依托单位：
SEATTLE CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10687155
关键词：
37 weeks gestation Amniotic Fluid Bacteria Bacterial Infections Bacterial Model Bioinformatics Birth Catheterization Cells Cesarean section Chorionic villi Chronic Clinical Computer Models Control Groups Data Decidua Dimensions Early identification Event Fetus Flow Cytometry Gene Expression Gene Proteins Genetic Transcription Hemolysin Histopathology Host Defense Hour Human Immune Immune Tolerance Immune response Immune system Immunohistochemistry Immunologics Infection Inflammation Inflammatory Response Injury Invaded Lead Link Maps Maternal-Fetal Exchange Membrane Metadata Methods Microbe Modeling Mutation Nature Neonatal Mortality Organism Pathogenicity Pathway interactions Peripheral Blood Mononuclear Cell Phase Placenta Population Pregnancy Premature Birth Premature Labor Protein Array Resolution Saline Sampling Signal Transduction Signaling Protein Streptococcal Infections Streptococcus Group B Time Transcription Repressor Uterus Virulent Woman adverse pregnancy outcome amniotic cavity cell type combat cytokine early onset experimental study fetal fetal blood gene regulatory network immune activation innovation intraamniotic infection microbial myometrium neonatal death neonatal infection neonatal morbidity nonhuman primate pathogen placental infection pregnant prevent programs reproductive tract response single-cell RNA sequencing stillbirth therapeutic development transcriptome

项目摘要

PROJECT SUMMARY/ABSTRACT Intra-amniotic infection and inflammation remain a significant cause of preterm birth, stillbirth and neonatal morbidity and mortality. The objective of this proposal is to define early maternal and placental immune responses that are critical for resolution of bacterial infections at the maternal-fetal interface. Elucidation of immune events occurring at the maternal-fetal interface in human pregnancy is complicated by the inaccessibility of maternal and fetal compartments, which also imposes limitations on our understanding of the nature of the invading organism and cell types directing bacterial clearance. We have overcome these challenges by using a unique chronically catheterized pregnant nonhuman primate (NHP) model that closely emulates human pregnancy. In this proposal, we will elucidate early immune mechanisms that result in bacterial clearance and define the key immune cell-types and host defense networks that protect the fetus from invasive bacterial infections. We will use the established NHP model of GBS infection to study bacterial clearance at the maternal-fetal interface using innovative methods including: 1) multidimensional flow cytometry to quantitate immune cell populations at the maternal-fetal interface, 2) single cell RNA-Seq to generate a transcriptional map of cell types and regulatory gene networks, 3) reverse phase protein array to analyze signalling cascades and host translational networks and 4) sophisticated computational modelling to link clinical metadata (e.g. bacterial burden, peak uterine activity) with single cell RNA-Seq and protein array data. The proposed aims will thus establish the temporal and spatial nature of immune responses and host transcriptional and translational networks essential for bacterial clearance at the maternal-fetal interface during pregnancy.

项目总结/文摘