CYTOKINES, ENTERIC INFECTION AND MUCOSAL IMMUNITY

细胞因子、肠道感染和粘膜免疫

• 批准号: 3733003
• 负责人: MARTIN F KAGNOFF
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3733003
• 关键词: Giardia; Salmonella; antibody formation; cell free system; cytokine; gastrointestinal infection; host organism interaction; immunoglobulin A; interleukin 4; interleukin 5; laboratory mouse; lipopolysaccharides; mucosal immunity; polymerase chain reaction; tissue /cell culture; tritium

Cytokines transmit signals important for communication among cells of the immune system and between cells of the immune system and other cells. Within the immune system, cytokines play a major role in B and T cell growth and differentiation, including the growth and differentiation of IgA B cells. Relevant to the proposed studies, we have previously demonstrated that interleukin-5 (IL-5) has activity as a late acting IgA B cell differentiation factor. This Project has three Specific Aims. The first Aim is to define the molecular mechanism by which cytokines such as IL-5 and bacterial products such as lipopolysaccharide (LPS) upregulate IgA production. In initial studies, we have established a model system for studying cytokine or LPS stimulated IgA secretion. Studies in the next Project period will define the molecular mechanisms important for the regulated expression of IgA production in this model system. Parasites and bacterial pathogens in the intestine are in contact with and invade intestinal epithelial cells. Cytokines produced by intestinal epithelial cells in response to enteric parasites and bacterial pathogens may play an important role as an early signaling system to adjacent and underlying cells of the immune system following infection. The second Aim of this Project will be to characterize the cytokines produced by intestinal epithelial cells in response to infection with the bacterial pathogen S. dublin and the parasite G. lamblia. These studies build on our initial finding that intestinal epithelial cells constitutively produce cytokines and can be stimulated to upregulate cytokine production in response to physiologic agonists. Peyer's patches are a major site for the entry, replication and persistence of bacterial pathogens, such as Salmonella, in the intestine. Moreover, the constellation of cytokines produced by cells in Peyer's patches, as well as in the mesenteric lymph nodes in response to enteric bacterial infection can determine the hosts' susceptibility and resistance to infection, and the outcome of infection. Therefore, the third Aim of these studies is to define the role specific constellations of cytokines produced in Peyer's patches and mesenteric lymph nodes play in determining host susceptibility or resistance to infection with the enteric pathogen S. dublin. Together, these studies will provide important new information regarding the importance of intestinal epithelial cells and the intestinal mucosal immune system in host resistance to bacterial and parasitic pathogens.

细胞因子传递对于细胞间通讯重要的信号 免疫系统和免疫系统的细胞与其他细胞之间的相互作用。 在免疫系统中，细胞因子在B和T细胞中起主要作用。 生长和分化，包括 IgA B细胞。 与建议的研究有关，我们先前已 表明白细胞介素-5（IL-5）具有作为迟效IgA的活性， B细胞分化因子。 该项目有三个具体目标。 第一个目的是确定细胞因子 如IL-5和细菌产物如脂多糖（LPS）， 上调IgA的产生。 在初步研究中，我们建立了一个 用于研究细胞因子或LPS刺激的IgA分泌的模型系统。 下一个项目期间的研究将确定分子机制 重要的是在这个模型中调节IgA的表达 系统 肠道中的寄生虫和细菌病原体在 接触并侵入肠上皮细胞。 产生的细胞因子 肠道上皮细胞对肠道寄生虫的反应， 细菌病原体可能在早期信号传导中发挥重要作用， 免疫系统的邻近和底层细胞， 感染 本项目的第二个目标是描述 由肠上皮细胞产生的细胞因子， 感染细菌病原体S. dublin和寄生虫G. 兰布利亚。 这些研究建立在我们最初发现的基础上， 上皮细胞组成性地产生细胞因子， 以响应生理激动剂而上调细胞因子的产生。 派伊尔斑是进入、复制和 细菌病原体，如沙门氏菌，在肠道中的持续存在。 此外，Peyer's细胞产生的细胞因子群 补丁，以及在肠系膜淋巴结，以响应肠 细菌感染可以决定宿主的易感性， 对感染的抵抗力和感染的结果。 因此 这些研究的第三个目的是定义特定于角色的星座 派尔集合淋巴结和肠系膜淋巴结产生的细胞因子 在确定宿主对感染的易感性或抵抗力方面， 肠道致病菌S.都柏林 这些研究将提供 关于肠道重要性的重要新信息 上皮细胞和宿主肠粘膜免疫系统 对细菌和寄生病原体的抗性。