Regulation by Botanicals of Pathogen-Specific Immune Def

植物药被认为是通过刺激哺乳动物的免疫系统来增强对感染病原体的防御能力。虽然有证据支持紫锥菊、黄芪、块茎、美塔克提取物和TJ-48对呼吸道和肠道感染的免疫抵抗力的有益影响，但潜在的免疫机制仍不清楚。在这个项目中，我们将研究这些植物药对小鼠对三种典型病原体：单核细胞增生性李斯特菌、牛分枝杆菌和致病霉菌烟曲霉菌的先天和获得性免疫反应的影响。单核细胞增多性乳杆菌是一种革兰氏阳性细菌，在摄入受污染的食物后通过胃肠道获得，并可传播到脾和肝脏。另一方面，烟曲霉菌和牛分枝杆菌是通过吸入感染的，虽然主要感染肺部，但也传播到其他器官。具体目的1测量口服植物摄入对单核细胞增多性乳杆菌、烟曲霉菌和牛分枝杆菌从主要感染部位和传播部位清除的影响。这些研究还将 确定植物药是否限制细菌或真菌传播的程度或严重程度。特定目的2衡量植物药物对这三种病原体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在感染肺、脾和肝脏中的募集以及炎性细胞因子和趋化因子的诱导。特定目的3衡量植物类药物对抗原特异性T细胞感染反应的影响。我们将描述CD4和CDS T细胞反应的特征，特别关注T细胞的增殖、分化和记忆的形成。我们将使用高度定量的分析方法来衡量在活动性感染的情况下植物药物对免疫参数的影响。在……里面 除了确定这些植物是否对抗微生物免疫有有益影响外，我们的研究还可能为了解它们的活性机制提供依据。

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.