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CMV infection impact on placental immunometabolism and fetal immunity

CMV感染对胎盘免疫代谢及胎儿免疫力的影响

基本信息

批准号：
10536197
负责人：
Amitinder Kaur
金额：
$ 42.47万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10536197
关键词：
Acute Adaptive Immune System Affect Amniotic Fluid Animal Model B-Lymphocytes Biological Biological Assay Biological Markers Biological Response Modifiers Birth Blood Bone Marrow Breeding Cells Cellular Immunology Cesarean section Child Childhood Chronic Communicable Diseases Comparative Study Cytomegalovirus Cytomegalovirus Infections Enrollment Epigenetic Process Epilepsy Exposure to Fetal Development Fetal Tissues First Pregnancy Trimester Flow Cytometry Genetic Genus Hippocampus Grant Human Immune Immune system Immunocompetent Immunologics Impaired cognition Infant Infection Inflammation Inflammatory Knowledge Leukocytes Life Lymphocyte Macaca Macaca mulatta Maternal Exposure Maternal-Fetal Exchange Maternally-Acquired Immunity Mediating Metabolic Metabolic Pathway Metabolism Mitogens Modeling Modification Monitor Monozygotic twins Mus Natural Immunity Natural Killer Cells Newborn Infant Outcome PTPRC gene Phenotype Population Population Study Pregnancy Primary Infection Primates Regulatory T-Lymphocyte Reporting Research Rhesus Role Second Pregnancy Trimester Seroprevalences Spleen Stains T-Lymphocyte Thymus Gland Vaccination Virus Diseases Woman XCL1 gene adaptive immunity congenital cytomegalovirus congenital infection cytokine disability fetal fetal blood fetal immunity fetal programming hearing impairment immune function imprint in utero insight metabolic abnormality assessment metabolomics monocyte motor impairment nonhuman primate novel pregnant prospective seropositive transcriptome sequencing transcriptomics transmission process young adult

项目摘要

PROJECT SUMMARY/ABSTRACT Cytomegalovirus (CMV) is a ubiquitous species-specific betaherpesvirus that results in life-long persistent asymptomatic infection in an immunocompetent host. Human CMV (HCMV) is the most common infectious cause of congenital infection, complicating 40,000 births in the U.S. annually. In utero CMV transmission occurs in 33-50% of pregnant CMV-seronegative women with primary infection; it also occurs after non-primary infection in pregnant CMV-seropositive women so that regions of high CMV seroprevalence account for a major part of the global burden of congenital CMV. Studies in mice and humans have shown that CMV has profound effects on both the innate and adaptive immune system. However, there is a gap in knowledge of when CMV imprints the immune system and whether maternal CMV infection during pregnancy can affect fetal development and immunity even in the absence of CMV transmission. In this grant, our aim is to study the effect of maternal exposure to CMV infection on fetal immunity using a biologically relevant rhesus macaque nonhuman primate (NHP) animal model of HCMV. We hypothesize that maternal exposure to CMV infection during pregnancy induces perturbation of cellular metabolism that adversely affect immune cell populations utilizing common metabolic pathways, leading to (i) hitherto unrecognized impact of CMV-mediated metabolic dysregulation on innate and adaptive immunity at the maternal-fetal interface, and (ii) epigenetic modifications and functional effects on fetal T and B lymphocytes, monocytes and NK cells. We will utilize a combined approach of cellular immunology assays, transcriptomics and metabolomics to investigate the effect of CMV infection on placental immunometabolism and fetal immunity in the NHP model. Our specific aims are: #1. To investigate the effect of chronic maternal CMV infection on placental immunometabolism and fetal immunity; and #2. To determine the effect of experimental primary CMV infection during pregnancy on placental immunometabolism and fetal immunity.

项目总结/文摘