LISTERIA PROTEINS EFFECTS ON CELL FUNCTION

李斯特菌蛋白质对细胞功能的影响

• 批准号: 2672561
• 负责人: TERRY A POTTER
• 金额: $ 25.28万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2672561
• 关键词: Listeria; bacterial proteins; biological signal transduction; biological transport; cell line; complement receptor; host organism interaction; hybrid cells; laboratory mouse; leukocyte adhesion molecules; macrophage; phagocytosis; protein purification; protein tyrosine kinase; receptor binding; receptor expression; vesicle /vacuole

DESCRIPTION (Adapted from applicant's abstract): The bacterium Listeria monocytogenes (LM) is a widespread, food borne pathogen that is responsible for periodic outbreaks of disease, causing gastrointestinal disease, sepsis, and in some cases, fatal meningitis. Listeriosis is often associated with an immunocompromised state, and in AIDS patients, it occurs at an incidence approximately 300 times greater than that found in the non-AIDS population. LM is taken up by different cells including macrophages. Upon internalization by macrophages, the bacterium can have two possible fates: (1) It can escape into the cytoplasm where it can replicate and subsequently invade other cells; (2) It remains within a phagocytic vesicle and is killed. They have obtained preliminary evidence which suggests that the pathway leading to either of these two possible outcomes is dictated by the mode of entry of the bacterium into the macrophage. If LM is taken up via the receptor for the third complement component (CR3), it does not escape into the cytoplasm and is killed. If LM enters a macrophage by binding of the bacterial internalin A (InlA) molecule to an as-yet unidentified surface molecule on the macrophage, the bacterium escapes into the cytoplasm and replicates. By analogy to the uptake of other bacteria, it is likely that the signal transduction events associated with the cell surface receptor molecules are initiated upon binding of LM to the macrophage. In this proposal they will conduct experiments to test the hypothesis that LM that enter a macrophage via interaction between InlA and its receptor will not be killed by the macrophage. First, they will define the role of In1A in binding, phagocytosis, and killing of LM by listericidal versus nonlistericidal macrophages. Second, they will delineate the molecular events within macrophages resulting from interaction between LM In1A and its putative macrophage receptor. They will define the signal transduction events which occur following binding of LM to the putative In1A receptor, and compare them to events initiated upon binding of LM to CR3. Third, they will attempt to identify, characterize and isolate the In1A receptor. These experiments should provide valuable information on the interaction of LM with phagocytic cells and may provide insights into the phagocytosis and killing of other intracellular bacteria.

描述（改编自申请人的摘要）：李斯特菌 单核细胞增生李斯特菌 (LM) 是一种广泛存在的食源性病原体， 用于周期性爆发疾病，导致胃肠道疾病、败血症， 在某些情况下，会导致致命的脑膜炎。 李斯特菌病通常与 免疫功能低下的状态，在艾滋病患者中，它的发生率很高 大约是非艾滋病人群的 300 倍。 LM 被包括巨噬细胞在内的不同细胞吸收。 之上 被巨噬细胞内化后，细菌可能有两种可能的命运： (1) 它可以逃入细胞质，在那里进行复制，随后 侵入其他细胞； (2)它保留在吞噬囊泡内并且 被杀了。 他们已获得初步证据表明 导致这两种可能结果之一的途径由 细菌进入巨噬细胞的方式。 如果 LM 被占用 第三补体成分（CR3）的受体，它不会逃脱 进入细胞质并被杀死。 如果 LM 通过结合进入巨噬细胞 将细菌内素 A (InlA) 分子附着到尚未识别的表面 巨噬细胞上的分子，细菌逃逸到细胞质中 复制。 通过类比其他细菌的吸收，很可能 与细胞表面受体相关的信号转导事件 分子在 LM 与巨噬细胞结合后启动。 在这个提案中，他们将进行实验来检验以下假设： 通过 InlA 与其受体之间的相互作用进入巨噬细胞的 LM 不会被巨噬细胞杀死。 首先，他们将定义角色 In1A 与杀李斯特菌对 LM 的结合、吞噬和杀伤作用 非李斯特菌巨噬细胞。 其次，他们将描述分子 LM In1A 与其相互作用导致巨噬细胞内发生事件 假定的巨噬细胞受体。 他们将定义信号转导 LM 与假定的 In1A 受体结合后发生的事件， 并将它们与 LM 与 CR3 结合时引发的事件进行比较。 第三，他们 将尝试识别、表征和分离 In1A 受体。 这些 实验应该提供关于 LM 相互作用的有价值的信息 与吞噬细胞一起，可以提供对吞噬作用和 杀死其他细胞内细菌。