Investigating immumomodulatory mechanisms of probiotics

研究益生菌的免疫调节机制

• 批准号: 312482-2013
• 负责人: Kim, SungOuk
• 金额: $ 3.13万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630109
• 关键词: Investigating; immumomodulatory; mechanisms; probiotics

Commensal microbes live inside the host in symbiosis. Probiotics are live commensals that have been used for centuries to replenish normal or beneficial gut and urogenital microflora. Long-term objectives of my research program are to understand how the host maintains immunological symbiosis with commensals and what immunological effects probiotics have on the host. During the last 5 years of NSERC support, our research program has focused on unraveling the mechanisms of the host cells in sensing bacterial probiotics and their effects on the host immune responses. We have demonstrated that the probiotic strain of Lactobacillus rhamnosus GR1 (GR1) and its secreted products have immunomodulatory effects on macrophages, dendritic cells, intestinal lamina propria cells and placental trophoblasts. GR1 as well as other strains of Lactobacillus rhamnosus preferentially and potently produce the immunomodulatory cytokine granulocyte colony-stimulating factor (G-CSF) in these cells, which may play important roles in maintaining immunological homeostasis of intestine and placenta. This research proposal is to further study the cellular and signaling mechanisms by which GR1, GR1-secreted factor(s) and G-CSF in modulating macrophage differentiation, activation and survival. The followings are specific aims of the study:Aim 1: Identify/purify the GR1-factor(s), and examine its/their signaling and epigenetic mechanisms responsible for preferential production of G-CSF in macrophages. Aim 2. Examining the role and mechanisms of G-CSF in macrophage differentiation and survival in bone marrow cells, THP-1 cells and the intestine. The proposed study will provide detailed information on how lactobacilli modulate macrophage activation and how G-CSF highly produced by lactobacillus-exposed macrophages affects myeloid cell differentiation and cell survival. Overall, these studies will unravel how commensals and probiotics modulate the host immune system and maintain symbiosis in the host.

共生微生物以共生的方式生活在宿主体内。益生菌是几个世纪以来一直用于补充正常或有益的肠道和泌尿生殖道微生物菌群的活益生菌。我的研究计划的长期目标是了解宿主如何维持与益生菌的免疫共生关系，以及益生菌对宿主的免疫作用。在NSERC支持的过去5年中，我们的研究计划专注于揭示宿主细胞在感知细菌益生菌及其对宿主免疫反应的影响方面的机制。我们已经证明，益生菌菌株鼠李糖乳杆菌GR 1（GR 1）及其分泌产物对巨噬细胞，树突状细胞，肠固有层细胞和胎盘滋养层细胞具有免疫调节作用。GR 1和其他鼠李糖乳杆菌一样，在这些细胞中优先产生免疫调节细胞因子粒细胞集落刺激因子（G-CSF），可能在维持肠道和胎盘的免疫稳态中发挥重要作用。本研究拟进一步研究GR 1、GR 1分泌因子和G-CSF对巨噬细胞分化、活化和存活的细胞和信号转导机制。以下是本研究的具体目的：目的1：鉴定/纯化GR 1-因子，并检查其/其信号传导和表观遗传机制，负责在巨噬细胞中优先产生G-CSF。目标2.检查G-CSF在骨髓细胞、THP-1细胞和肠中巨噬细胞分化和存活中的作用和机制。拟议的研究将提供有关乳酸杆菌如何调节巨噬细胞活化以及由乳酸杆菌暴露的巨噬细胞高度产生的G-CSF如何影响骨髓细胞分化和细胞存活的详细信息。总的来说，这些研究将揭示益生菌和益生菌如何调节宿主免疫系统并维持宿主的共生关系。