LISTERIA PROTEINS EFFECTS ON CELL FUNCTION

李斯特菌蛋白质对细胞功能的影响

• 批准号: 6169282
• 负责人: TERRY A POTTER
• 金额: $ 26.82万
• 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/6169282
• 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（改编自申请人摘要）：李斯特菌 单核细胞增多症（LM）是一种广泛的食源性病原体， 用于周期性疾病爆发，引起胃肠道疾病，败血症， 在某些情况下，致命的脑膜炎。 李斯特菌病通常与 一种免疫功能低下的状态，在艾滋病患者中， 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。 后 通过巨噬细胞的内化，细菌可以有两种可能的命运： (1)它可以逃到细胞质中，在那里它可以复制， 侵入其他细胞;（2）它留在吞噬囊泡内， 杀了 他们获得的初步证据表明， 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通过 第三补体成分（CR 3）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 将细菌内分泌蛋白A（InlA）分子粘附到一个尚未鉴定的表面上 当巨噬细胞上的一个分子被破坏时，细菌逃逸到细胞质中， 复制品。 与其他细菌的吸收类似， 与细胞表面受体相关的信号转导事件 分子在LM与巨噬细胞结合时启动。 在这个建议中，他们将进行实验来检验假设， 通过InlA及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，他们将确定 In 1A在通过杀李斯特菌与 非杀李斯特菌的巨噬细胞 其次，他们将描绘出 巨噬细胞内的事件是由LM In 1A及其 假定的巨噬细胞受体。 它们将定义信号传导 LM与推定的In 1A受体结合后发生的事件， 并将它们与LM与CR 3结合后引发的事件进行比较。 三是 将尝试识别、表征和分离In 1A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，并可能提供洞察吞噬作用， 杀死其他细胞内细菌。