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Schistosoma Mansoni Infection During Pregnancy: Dissecting the Implications to Fetal Immunity

怀孕期间曼氏血吸虫感染：剖析对胎儿免疫的影响

基本信息

批准号：
10331295
负责人：
Keke Celeste Fairfax
金额：
$ 46.25万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-02-01 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10331295
关键词：
Address Africa Antigen Presentation Antigen-Presenting Cells Antigens Attenuated B-Lymphocytes BCG Live Cell Compartmentation Childhood Chronic Communicable Diseases Complement 3d Receptors Country Development Diagnosis Diphtheria Environment Exposure to Family Female of child bearing age Fetal Development Fetus Frequencies Future Generations Goals Health Professional Helminth Antigens Helminths Hepatitis B Homeostasis Human Immune Immune response Immune system Immunity Immunization Immunologics Infant Infection Interleukin-4 Life Memory Memory B-Lymphocyte Modeling Mothers Mus Neonatal Outcome Parasites Parasitic infection Pathologic Peripheral Pharmacotherapy Platyhelminths Play Population Positioning Attribute Praziquantel Pregnancy Pregnant Women Public Health Recommendation Reporting Research Research Personnel Resources Risk Role Savings Schistosoma Schistosoma mansoni Schistosoma mansonii infection Schistosomiasis Signal Transduction Stromal Cells Structure of germinal center of lymph node T-Lymphocyte TNF gene Testing Tetanus Th2 Cells Tuberculosis Vaccines Woman early childhood fetal immunity helminth infection immunogenic immunoregulation improved in utero lymph nodes mouse model neglected tropical diseases offspring postnatal preconditioning pregnant prenatal prenatal exposure response treatment strategy vaccine efficacy vaccine-induced immunity

项目摘要

Maternal helminth infections have been implicated in the reduced efficacy of critical life-saving neonatal and childhood immunizations. Approximately 40 million women of childbearing age are at risk for schistosomiasis and at least 10 million women in Africa have schistosomiasis during pregnancy, yet little is known about the impact of prenatal exposure on the immune responsiveness of offspring. Findings from previous studies indicate that a fetus can be exposed to helminth antigens in utero, so the high frequency of schistosomiasis in this population represents a significant potential public health problem. The WHO recently recommended anthelminthic treatments for all pregnant women who test helminth positive; however, very few studies have evaluated the immunological impact of drug treatment on either the mother or the fetus. Anthelminthic treatment and the resultant release of parasite antigens have the potential to sensitize a fetus in much the same way that natural infection does. Given the potentially serious adverse pathological and immunological consequences of both maternal infection and anthelminthic treatment, it is critical that we understand the immunological consequences of prenatal helminth infection, so that appropriate recommendations can be formulated to address any issues with current practices and, ultimately, help to improve immune responses in infants in resource-poor countries. Our objective in this proposal is to determine the immunological mechanism(s) through which prenatal S. mansoni infection modulates the homeostatic immune environment, and the effect this immune-modulation has on post-natal immune responses to antigenic challenge in a mouse model of maternal S. mansoni infection. Our central hypothesis is that in utero exposure to S. mansoni antigens reduces the steady-state expression of the co-stimulatory molecules CD21/35, and preconditions lymph nodes in the developing fetus towards a muted Th2-skewed immune response following postnatal immunization with immunologically unrelated antigens. We propose three specific aims to test this: 1) Define the mechanism(s) by which prenatal exposure of mice to S. mansoni infection modulates postnatal peripheral lymph node homeostasis; 2) Define the mechanism(s) by which prenatal exposure to S. mansoni infection modulates postnatal cellular immune responses to unrelated antigenic challenge; 3) Determine the consequences of anthelminthic treatment of infected pregnant mice on postnatal vaccine-induced immunity of offspring. At the completion of these studies, we expect to have identified key immunological mechanisms that underlie reduced immunity in offspring born to mothers infected with S. mansoni. It is likely these mechanisms will include reduced antigen presentation ability and preconditioning of antigen presenting cells and the T cell compartment towards priming a Th2 response; however even if it is not, we expect to have identified key mechanisms underlying reduced immunity. Successful completion of these studies can be expected to have a potentially important future positive impact on strategies for treatment of helminth-infected pregnant women.

母体蠕虫感染与关键的挽救新生儿生命的药物疗效降低有关