Regulation by Botanicals of Pathogen-Specific Immune Defense

植物药对病原体特异性免疫防御的调节

• 批准号: 7641077
• 负责人: Eric G. Pamer
• 金额: $ 14.3万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7641077
• 关键词: Antigens; Aspergillus fumigatus; Bacteria; Biological Assay; Botanicals; Breathing; CD4 Positive T Lymphocytes; Canned Foods; Disease; Echinacea (Asteraceae); Echinacea Preparation; Gastrointestinal tract structure; Genus Mycobacterium; Goals; Gram-Positive Bacteria; Hand; Immune; Immune response; Immune system; Immunity; Immunocompromised Host; Infection; Inflammatory; Inflammatory Response; Ingestion; Intestines; Intravenous; Kidney; Laboratories; Light; Listeria monocytogenes; Liver; Lung; MHC Class I Genes; Maitake; Measures; Memory; Methods; Modeling; Molds; Mus; Mycobacterium bovis; Oral; Organ; Personal Satisfaction; Phenotype; Production; Range; Regulation; Reproduction spores; Route; Severities; Site; Small Intestines; Spleen; Staining method; Stains; T-Cell Proliferation; T-Lymphocyte; TJ48; Talus; Testing; Tumeric; antimicrobial; body system; chemokine; cytokine; enzyme linked immunospot assay; immune resistance; improved; in vivo; infectious disease model; insight; intestinal epithelium; lymph nodes; microbial; monocyte; neutrophil; pathogen; respiratory; response

Botanicals are postulated to augment defenses against infectious pathogens by stimulating the mammalian immune system. While there is evidence supporting the beneficial impact of Echinacea, Astragalus, Tumeric, Maitake Extract and TJ-48 on immune resistance to respiratory and intestinal infections, the underlying immune mechanisms remain undefined. In this project we will investigate the effect of these botanicals on murine innate and adaptive immune responses against three well characterized pathogens: Listeria monocytogenes, Mycobacterium bovis and the pathogenic mold, Aspergillus fumigatus. L. monocytogenes, a Gram-positive bacterium, is acquired via the gastrointestinal tract after ingestion of contaminated food and can disseminate to spleen and liver. A. fumigatus and M. bovis, on the other hand, are acquired by inhalation and, while primarily infecting the lung, also disseminate to other organs. Specific aim 1 measures the impact of oral botanical ingestion on the clearance of L. monocytogenes, A. fumigatus and M. bovis from the primary site of infection and from sites of dissemination. These studies will also determine whether botanicals limit the extent or severity of bacterial or fungal dissemination. Specific aim 2 measures the impact of botanicals on innate inflammatory responses to infection by these three pathogens. We will quantify neutrophil and monocyte recruitment and the induction of inflammatory cytokines and chemokines in infected lungs, spleens and livers. Specific aim 3 measures the impact of botanicals on antigen specific T cell responses to infection. We will characterize CD4 and CDS T cell responses, focusing specifically on T cell proliferation, differentiation and memory formation. We will employ highly quantitative assays to measure the impact of botanicals on immune parameters in the context of active infection. In addition to determining whether these botanical have salutary effects on antimicrobial immunity, our studies are likely to provide insight into their mechanism of activity.

假定植物性可以通过刺激哺乳动物免疫系统来增强防御性病原体的防御能力。虽然有证据支持紫锥菊，阿斯托拉素，肿瘤，梅塔克提取物和TJ-48对呼吸道和肠道感染的免疫耐药性的有益影响，但潜在的免疫机制仍然不确定。在这个项目中，我们将研究这些植物因素对三种特征性病原体的鼠生和适应性免疫反应的影响：单核细胞增生李斯特菌，牛分枝杆菌和致病性霉菌烟曲霉。单核细胞增生李斯特氏菌是一种革兰氏阳性细菌，是在摄入受污染的食物后通过胃肠道获得的，可以将其传播到脾脏和肝脏。另一方面，A. fumigatus和M. Bovis是通过吸入而获得的，而主要感染肺部也将其传播到其他器官。具体目标1测量口腔植物摄入对单核细胞增生李斯特氏菌，富米曲霉和牛乳杆菌清除的影响，从原发性感染部位和传播部位。这些研究也将 确定植物会是否限制细菌或真菌传播的程度或严重程度。具体目标2测量了植物对这三种病原体对感染的先天炎症反应的影响。我们将量化中性粒细胞和单核细胞募集，并诱导感染的肺，脾脏和肝脏中炎性细胞因子和趋化因子。特定目标3测量植物对抗原特异性T细胞对感染的影响的影响。我们将表征CD4和CD T细胞反应，专门针对T细胞增殖，分化和记忆形成。我们将使用高度定量的测定法来衡量植物对免疫参数的影响。在 除了确定这些植物学是否对抗菌免疫具有巨大影响，我们的研究可能会洞悉其活性机理。