INFLAMMATION IN RESISTANCE TO BACTERIAL INFECTION

由兼性细胞内病原体引起的感染仍在继续 在美国是一个严重的健康问题， 遍布世界各地。免疫治疗策略的研究 因此，抗击这些感染将具有相当大的意义。 利益。小鼠李斯特菌病已被证明是一种方便的， 可重现的、信息量极大的实验室模型 黄曲霉毒素抗感染免疫调节作用的研究 兼性细胞内病原体。相当多的证据表明 由我们的实验室和其他与抗李斯特菌有关的机构提供 抵抗与宿主的能力，迅速动员足够的 对入侵细菌的炎症反应。双重奏 T淋巴细胞在炎症调节中的作用 响应性和抗菌性由以下指标表示 李斯特菌免疫T细胞的适应性转移研究表明 L3T4+T细胞介导炎性细胞的聚集 体内和Lyt2+T细胞是表达抗菌素所必需的 抵抗。尽管这些研究提供了相当多的信息， 他们没能证明细胞间的相互作用 当个人第一次遇到入侵的兼职人员时 细胞内病原体。在拟议的研究中，我们将操纵 抗小鼠T细胞亚群单抗体内实验研究 L3T4和Anit Lyt2抗体，然后确定治疗效果 这些治疗方法对炎症反应性和 抗菌素耐药性。这些T细胞产生的可溶性因子 将在体内评估细胞的促炎作用 以及它们对巨噬细胞抗菌活性的影响 体外培养。李斯特菌免疫Lyt2+T细胞可能的细胞毒作用 针对利特里亚感染的巨噬细胞的细胞将被研究为 一种潜在的机制解释了由 这些细胞在体内。除了提供信息， 进一步阐明了我们对T细胞介导的 对兼性病原体的抗性，这一项目的结果 也将与人类李斯特菌病的发病机制密切相关， 它已经迅速成为一个重大的公共卫生问题 由于摄入了受李斯特菌污染的乳制品。

Infections caused by facultative intracellular pathogens continue to be a significant health problem in the United States and througout the world. Immunotherapeutic strategies for combatting these infections would therefore be of considerable benefit. Murine listeriosis has proven to be a convenient, reproducible, and extremely informative laboratory model for studying immuno-regulation of resistance to infection by facultative intracellular pathogens. Considerable evidence has been provided by our laboratory and others linking anti-listeria resistance with the host's ability to rapidly mobilize an adequate inflammatory response against the invading bacteria. The dual role of T lymphocytes in the regulation of inflammatory responsiveness and antibacterial resistance has been indicated by adpotive transfer studies of listeria-immune T cells which showed that L3T4+ T cells mediate accumulation of inflammatory cells in vivo and Lyt2+ T cells are required for expression of antibacterial resistance. Although these studies have been quite informative, they fail to demonstrate the cellular interactions that occur in vivo when an individual first encounters an invading facultative intracellular pathogen. In the proposed study we will manipulate mouse T cell subsets in vivo by administration of monoclonal anti- L3T4 and anit Lyt2 antibodies and then determine the effect of these treatments on inflammatory responsiveness and antibacterial resistance. Soluble factors produced by these T cells will be assessed for their pro-inflammatory effects in vivo and for their influence on macrophage antibacterial activity in vitro. The possible cytotoxic actio of listeria-immune Lyt2+ T cells against literia-infected macrophages will be investigated as a potential mechanism explaining the protection mediated by these cells in vivo. Besides providing information that will further illuminate our general understanding of T cell-mediated resistance to facultative pathogens, the resuslts of this project will also be germane to the pathogenesis of human listeriosis, which has rapidly emerged as a significant public health problem due to ingestion of listeria-contaminated dairy products.