Innate immunity and dendritic cells in cryptosporidiosis

隐孢子虫病中的先天免疫和树突状细胞

基本信息

批准号：
7661516
负责人：
SAUL r TZIPORI
金额：
$ 38.98万
依托单位：
TUFTS UNIVERSITY BOSTON
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：
2006-08-15 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7661516
关键词：
Acute Address Age Bone Marrow Categories Cell Line Cells Chronic Cryptosporidiosis Cryptosporidium Cryptosporidium parvum Data Dendritic Cells Dendritic cell activation Development Diarrhea Drug Formulations Elements Enteral Epithelial Cells Event Exposure to Future Gastroenteritis Gene Expression Genetic Goals Human Immune Immune response Immune system Immunity Infection Interleukin-12 Intervention Intestines Invaded Knockout Mice Knowledge Laboratories Lead Life Ligands Link Matched Group Measures Methods Microarray Analysis Morbidity - disease rate Mus Natural Immunity Nature Pan Genus Parasites Phenotype Play Prevention Production Proteins Protozoa Receptor Signaling Recombinants Recovery Reporting Research Personnel Resistance Resistance Process Role Spleen Surface System TNFRSF5 gene Testing Toll-like receptors Up-Regulation Vaccine Adjuvant Vaccine Design base combat cytokine design effective therapy gut microflora human disease innovation monocyte mortality parasite invasion pathogen programs research study response ward wasting

Acute Address Age Bone Marrow Categories Cell Line Cells Chronic Cryptosporidiosis Cryptosporidium Cryptosporidium parvum Data Dendritic Cells Dendritic cell activation Development Diarrhea Drug Formulations Elements Enteral Epithelial Cells Event Exposure to Future Gastroenteritis Gene Expression Genetic Goals Human Immune Immune response Immune system Immunity Infection Interleukin-12 Intervention Intestines Invaded Knockout Mice Knowledge Laboratories Lead Life Ligands Link Matched Group Measures Methods Microarray Analysis Morbidity - disease rate Mus Natural Immunity Nature Pan Genus Parasites Phenotype Play Prevention Production Proteins Protozoa Receptor Signaling Recombinants Recovery Reporting Research Personnel Resistance Resistance Process Role Spleen Surface System TNFRSF5 gene Testing Toll-like receptors Up-Regulation Vaccine Adjuvant Vaccine Design base combat cytokine design effective therapy gut microflora human disease innovation monocyte mortality parasite invasion pathogen programs research study response ward wasting

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项目摘要

DESCRIPTION (provided by applicant): This application is in response to RFA-AI-05-042 on Innate Immunity to Category B protozoa of which Cryptosporidium spp rank among the most significant. Two species, C. hominis and C. parvum, are linked with human cryptosporidiosis, a serious cause of morbidity and mortality worldwide, and against which there is no effective therapy of prevention. Our goal is to elucidate the mechanisms by which immune cells initiate resistance against cryptosporidiosis with a view that a better understanding of the various components of the immune response will lead to development of effective vaccines and adjuvants to combat the infection in humans. Our central hypothesis is that dendritic cells recognize Cryptosporidium through Toll like receptor(s) which initiate the process of resistance against parasite invasion. We base this on the observations that: 1) dendritic cells sense pathogens through Toll-like receptors which lead to the initiation of adoptive immune responses, 2) proinflammatory cytokine IL-12, predominately produced by dendritic cells, is critical in controlling Cryptosporidium infection, and 3) bone marrow-derived CD40-positive cells are required for mice to clear C. parvum infection. Based on these observations, the specific aims are designed to investigate the innate immune response to cryptosporidiosis with a view to determining the mechanisms of Toll-like receptor signaling that lead to such responses, using both mice and human dendritic cells. The specific aims are to: 1) characterize the role of mouse dendritic cells in the innate immune response against C. parvum infection; 2) determine the nature of activation of human dendritic cells upon infection with C. parvum or C. hominis; 3) identify the Toll-like receptor used by Cryptosporidium and isolate TLR activating ligand(s) expressed by the parasite. The proposed studies will provide the basis for understanding the mechanisms of innate immune recognition and response to parasite invasion necessary for future design of vaccines and other methods of interventions.

描述（由申请人提供）：此申请响应RFA-AI-05-042对B类原生动物的先天免疫力，其cryptosporidium spp排名最重要。两个物种，hominis和parvum C. parvum，与人类隐孢子虫病有关，这是全球发病率和死亡率的严重原因，并且没有有效的预防治疗。我们的目标是阐明免疫细胞对隐孢子虫病的抗性的机制为了更好地理解免疫反应的各个组成部分，将导致有效的疫苗和辅助因素与人类感染作斗争。我们的中心假设是，树突状细胞通过像受体一样识别隐孢子虫，从而引发了抵抗寄生虫侵袭的过程。我们基于以下观察结果：1）树突状细胞通过类似Toll样受体感染病原体，导致产生过继的免疫反应，2）促炎细胞因子IL-12，主要由树突状细胞产生，主要由树突状细胞产生，至关重要的是在控制隐孢子虫感染方面至关重要。基于这些观察结果，具体目的旨在研究对隐孢子虫病的先天免疫反应，以确定使用小鼠和人类树突状细胞的Toll样受体信号传导的机制，从而导致这种反应。具体目的是：1）表征小鼠树突状细胞在先天性中的作用针对白梭菌感染的免疫反应； 2）确定在感染C. parvum或hominis感染后，人树突状细胞激活的性质； 3）确定由寄生虫表达的隐孢子虫和分离物TLR激活配体使用的Toll样受体。拟议的研究将为理解先天免疫识别的机制和对未来疫苗设计和其他干预方法所必需的寄生虫入侵的机制提供基础。