STRESS/BACTERIAL INTERACTIONS IN INFECTIOUS DISEASE

传染病中的压力/细菌相互作用

• 批准号: 6185549
• 负责人: MARK LYTE
• 金额: $ 8.64万
• 依托单位: MINNESOTA STATE UNIVERSITY, MANKATO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6185549
• 关键词: Clostridium; Enterobacteriaceae; bacterial disease; behavioral /social science research tag; catecholamines; host organism interaction; laboratory mouse; microorganism culture; microorganism growth; neuroendocrine system; norepinephrine; polymerase chain reaction; psychological stressor; psychoneuroimmunology; stress; virulence

DESCRIPTION (Applicant's abstract): The ability of stress to alter susceptibility to infectious challenge is currently believed to result from neuroendocrine modulation of immune responsiveness. The hypothesis evaluated in this application is that direct, nonimmune, interactions between the neuroendocrine system and the infecting organism are additionally responsible for stress-induced alterations in the pathogenesis of infectious disease. This hypothesis is based on the investigators' findings of catecholamine specific enhancement of in vitro and in vivo bacterial growth and increased expression of virulence factors. The first Specific Aim will establish the ability of the naturalistic, etiologically relevant stressor of social conflict to alter susceptibility in mice to infectious oral challenge with the primary model of human bacterial invasiveness, Yersinia enterocolitica. The second Specific Aim will examine the in vitro molecular mechanisms by which catecholamines influence the growth of Yersinia and the production of violence factors. These experiments, which include examination of norepinephrine-induced alterations in bacterial physiology and molecular fingerprinting, will provide a significant part of the mechanistic information necessary to dissect results from subsequent in vivo experiments. According to the third Specific Aim the use of both closed and open chamber implant methods will provide in vivo environments to identify whether stress-induced changes in bacterial pathogenesis are due to direct neuroendocrine-bacterial interactions (closed chamber). Preliminary data have demonstrated increased growth of Y. enterocolitica in closed implant chambers of stressed as compared to handled control animal thus supporting the hypothesis that direct neuroendocrine-bacterial interactions can occur in vivo. The fourth Specific Aim will utilize endocrine manipulated mice to determine the pathways participating in stress-induced alterations in infectious susceptibility. The fifth Specific Aim will examine whether the results obtained with the gram-negative bacterium Y. Enterocolitica are applicable to a gram-positive bacterium. These in vitro experiments will determine if the theory of direct neuroendocrine-bacterial interactions is applicable to other infectious agents. Collectively, the completion of the proposed experiments will establish a direct cause and effect relationship between the endocrinological and infectious aspects as a consequence of stress. The RSDA will provide the time necessary to develop the technical expertise and foster the collaborative efforts that are required for the rigorous testing of the theory of stress-bacterial interactions in infectious disease. These studies will thus provide insight into the pathogenesis of infectious disease by examining the ability of the infecting organism to actively respond to stress-induced alterations in neuroendocrine activity. This route significantly differs from the current psychoneuroimmunological approach in which alterations in infectious susceptibility are viewed to occur solely as a consequence of stress-induced alterations in the immune mechanisms responsible for defense against infection.

描述（申请人摘要）：压力改变 目前认为对感染性攻击易感性是由 免疫应答的神经内分泌调节。 的假设 在这个应用程序中评估的是，直接的，非免疫的，相互作用 神经内分泌系统和感染生物之间的联系 另外还负责应激诱导的发病机制改变 传染性疾病。 这一假设是基于调查人员的 在体外和体内的儿茶酚胺特异性增强的发现 细菌生长和毒力因子表达增加。 第一个具体目标将建立自然主义的能力， 社会冲突的病因相关应激源改变易感性 在小鼠中感染性口服攻击与人的主要模型 小肠结肠炎耶尔森氏菌。 第二个具体目标 将研究体外分子机制， 影响耶尔森菌的生长和暴力因子的产生。 这些实验，其中包括检查去甲肾上腺素诱导的 细菌生理学和分子指纹的改变， 提供必要的机械信息的重要部分， 分析随后的体内实验结果。 根据第三 具体目的：使用封闭腔和开放腔植入方法将 提供体内环境，以确定是否应力诱导的变化， 细菌致病是由于直接的神经内分泌-细菌 封闭腔（closed chamber）。 初步数据显示， Y.生长小肠结肠炎在封闭的植入物腔室的应力作为 与处理对照动物相比，因此支持以下假设： 直接的神经内分泌-细菌相互作用可在体内发生。 第四 Specific Aim将利用内分泌操作小鼠来确定 参与应激诱导的感染性细胞因子改变的途径 易感性 第五个具体目标将审查结果是否 用革兰氏阴性菌Y.小肠结肠炎适用 革兰氏阳性细菌的反应 这些体外实验将确定 神经内分泌-细菌直接相互作用的理论适用于 其他传染病。 总体而言，完成拟议的 实验将建立一个直接的因果关系， 内分泌和感染方面的压力。 的 RSDA将提供必要的时间来发展技术专长， 促进严格测试所需的协作努力 压力-细菌相互作用理论的核心。 这些 因此，研究将提供深入了解传染性疾病的发病机制， 通过检查感染生物体主动 对压力引起的神经内分泌活动的改变作出反应。 这 途径与目前的心理神经免疫学 一种将感染易感性的改变视为 仅仅是由于应激诱导的免疫系统改变而发生的。 负责防御感染的机制。