Regulation by Botanicals of Pathogen-Specific Immune Def

植物药被认为可以通过刺激哺乳动物的免疫系统来增强对传染性病原体的防御。虽然有证据支持紫锥菊、黄芪、莪术、灰竹提取物和TJ-48对呼吸道和肠道感染的免疫抗性的有益影响，但潜在的免疫机制仍不明确。在本项目中，我们将研究这些植物药物对小鼠先天免疫和适应性免疫反应的影响，以对抗三种特征明确的病原体：单核细胞增生李斯特菌、牛分枝杆菌和致病菌烟曲霉。单核增生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，并可传播到脾脏和肝脏。另一方面，烟曲霉和牛分枝杆菌是通过吸入获得的，虽然主要感染肺部，但也会传播到其他器官。具体目的1测量口服植物摄入对单核细胞增生乳杆菌、烟状芽胞杆菌和牛分枝杆菌从主要感染部位和传播部位清除的影响。这些研究也会

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.