Regulation by Botanicals of Pathogen-Specific Immune Def

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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.