权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Modulation of schistosome development by T cell signals

T 细胞信号对血吸虫发育的调节

基本信息

批准号：
7367900
负责人：
Stephen J Davies
金额：
$ 36.08万
依托单位：
HENRY M. JACKSON FDN FOR THE ADV MIL/MED
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-03-01 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7367900
关键词：
Accounting Address Affect Africa Animals Antigens Area Asia Bacteria Biological Biological Models CD4 Positive T Lymphocytes Cell Communication Cell Survival Cell physiology Cells Complex Condition Coupled Data Development Disease Disruption Foundations Genome Goals Helminths Human Human Resources IL2RA gene Immunity Immunocompetent Immunodeficient Mouse Immunotherapy Infection Infection prevention Integration Host Factors Interleukin-2 Intestines Laboratory Study Life Life Cycle Stages Liver Mediating Modeling Molecular Morbidity - disease rate Mus Outcome Parasites Parasitic Diseases Pathology Peace Corps Peptides Plastics Play Population Process Program Development Public Health Rate Reproduction Research Personnel Resistance development Role Schistosoma Schistosoma mansonii infection Schistosomatidae Schistosomiasis Services Signal Transduction South America Specificity Staging System T-Cell Development T-Lymphocyte Testing Therapeutic Tissues Transgenic Organisms Urinary system Vaccines Virus Visit base cytokine in vivo in vivo Model migration mortality mouse model novel strategies pathogen prevent programs prophylactic reconstitution response transmission process

项目摘要

Schistosomiasis, the parasitic disease caused by blood flukes of the genus Schistosoma, causes potentially serious liver, intestine and urinary system pathology in approximately 200 million people worldwide, resulting in significant morbidity and mortality. In addition to constituting a major public health concern for people living in endemic areas in South America, Africa and Asia, schistosomiasis is also a significant concern for U.S. service personnel, Peace Corps workers and civilians visiting regions where blood flukes are prevalent. High re-infection rates following treatment and the potential for development of resistance to the few effective chemotherapeutics for schistosomiasis has prompted efforts to develop vaccines that prevent infection and/or disease. While an effective vaccine has not yet been developed, evidence from field and laboratory studies indicate that CD4+ T cell responses will be critical components of the response induced by an effective vaccine. However, our studies using a murine model of schistosome infection have demonstrated that, paradoxically, schistosomes also require signals from host CD4+ T cells to complete their development normally, suggesting that blocking interactions between parasite and host T cells might provide a novel approach to interfering with parasite development. The long-term objective of our studies is to contribute to the development of new immunotherapies aimed at preventing schistosome development in the definitive human host, thus simultaneously preventing the pathology associated with schistosome infection and blocking parasite transmission. The overall aim of this study is to further our understanding of the role CD4+ T cells play in facilitating the development and reproduction of Schistosoma blood flukes. The specific aims of this study are (1) to determine whether the presence of CD4* T cells alone is sufficient to facilitate parasite development, (2) to determine whether CD4+ T cell responses to schistosome antigens are important in influencing the outcome of schistosome development, and (3) determine the role of the CD4+ T cell cytokine interleukin-2 (IL-2) in affecting the outcome of schistosome development. Specific aim 1 will be accomplished by examining schistosome infections in a transgenic mouse model where none of the animal's CD4+ T cells are able to respond to schistosome antigens because of their restricted specificity for an unrelated antigen. Specific aim 2 will be accomplished by selectively reconstituting immunodeficient mice with CD4+ T cells that can or cannot respond to schistosome antigens prior to infection and then examining the effect of activation with the appropriate antigen on parasite development. Specific aim 3 will be addressed by examining schistosome infection in IL-2-deficient mice.

血吸虫病是一种由血吸虫属的血吸虫引起的寄生虫病，具有潜在的致病性