Helminth Modulation of the Protective Immune Response to Tuberculosis

蠕虫对结核病保护性免疫反应的调节

• 批准号: 7323094
• 负责人: Julius Andrew Potian
• 金额: $ 2.5万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-19 至 2010-07-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7323094
• 关键词: Accounting; Acquired Immunodeficiency Syndrome; Acute-Phase Reaction; Address; Affect; Africa South of the Sahara; Asses; Awareness; Bacillus (bacterium); Cells; Cellular Immunity; Chronic; Developed Countries; Developing Countries; Development; Disease; Disease Progression; Disease susceptibility; Drug resistance; Effectiveness; Experimental Models; Generations; Goals; Granuloma; HIV; Helminths; Host resistance; Human; Immune; Immune response; Immunity; Immunohistochemistry; Immunology; Individual; Infection; Infection Control; Interleukin-13; Interleukin-4; Investigation; Life; Malaria; Memory; Modality; Modeling; Morality; Morbidity - disease rate; Mus; Mycobacterium tuberculosis; Nature; Nematoda; Nematode infections; Nippostrongylus; Parasites; Parasitic infection; Pathogenesis; Pathology; Polymerase Chain Reaction; Population; Prevalence; Production; Public Health; Southeastern Asia; T memory cell; Techniques; Testing; Time; Tuberculosis; Vaccine Therapy; chemotherapy; cytokine; design; immunoregulation; in vivo; innovation; insight; mouse model; pathogen; response; role model; vaccine development

DESCRIPTION (provided by applicant): Regions of the world that are endemic for tuberculosis (TB) are also endemic for helminthic infections. It is estimated that TB affects one-third of the world's population, with helminthic infections accounting for disease in over one quarter of the world's population. TB and helminthic infections pose a major public health concern, particularly in developing nations where the prevalence of both diseases is alarmingly high. Strategies aimed at combating parasitic infections may also help in control of the Big three killers: TB, HIV, and Malaria. Although it is known that protection to TB infection is dependant on development of a strong T helper (Th) 1 response, the effect of Th2 responses, elicited by helminths on the control of TB remains unclear. In this proposal we will use a mouse model of helminth/TB co-infection and real time PCR, immnohistochemistry, and flow cytometric techniques will be implemented to asses the effect of co-infection on bacterial burden, cytokine expression levels, and granuloma formation. The central goal of this proposal is to examine the mechanism for Th2 modulation of the protective immune response to TB infection and study its impact on the development of memory responses to re-infection in vivo. Overall we expect to obtain from these studies an insight into the factors that can modulate the Th1 protective immunity to TB. Successful completion of these studies will provide innovative strategies for vaccine development and also provide new modalities of modulating the immune response to shorten chemotherapy and/or overcome drug resistance. The specific aims that will address the goals of the proposal are: Aim 1 we will conduct in vivo infection studies to determine how helminth infections modulate the course of TB infection. Aim 2 of our study, we will determine the effect of co-infection in the development of effective memory T-cell responses to re-infection with TB.

描述（由申请人提供）：结核病（TB）的世界地区也是蠕虫感染的特有。据估计，结核病会影响世界人口的三分之一，蠕虫感染在全球人口的四分之一中占疾病。结核病和蠕虫感染引起了一个主要的公共卫生关注，尤其是在两种疾病患病率的发展中国家都令人震惊的是。旨在打击寄生虫感染的策略也可能有助于控制三大杀手：结核病，艾滋病毒和疟疾。尽管众所周知，对结核病感染的保护取决于强大的T助手（Th）1响应的发展，但蠕虫中产生的Th2反应的影响仍不清楚。在此提案中，我们将使用蠕虫/结核病共感染和实时PCR，IMMNO组织化学和流式细胞仪技术的小鼠模型来评估共同感染对细菌负担，细胞因子表达水平和肉芽肿的形成的影响。该提案的核心目的是检查对TB感染的保护性免疫反应的Th2调节机制，并研究其对体内重新感染记忆反应的发展的影响。总体而言，我们期望从这些研究中获得有关可以调节TH1保护性免疫力的因素。这些研究的成功完成将为疫苗开发提供创新的策略，还提供了调节缩短化学疗法和/或克服耐药性的免疫反应的新方式。解决该提案目标的具体目的是：目标1我们将在体内感染研究中进行研究，以确定蠕虫感染如何调节结核病感染的过程。我们研究的目标2，我们将确定共感染对有效记忆T细胞反应对重新感染的有效记忆反应的影响。