NaCl and Nuclear Factor of Activated T Cells 5 (NFAT5) in macrophage and granulocyte-driven antibacterial host defense

巨噬细胞和粒细胞驱动的抗菌宿主防御中的 NaCl 和活化 T 细胞核因子 5 (NFAT5)

• 批准号: 321687843
• 负责人: Professor Dr. Jonathan Jantsch
• 金额: --
• 依托单位: Institut für Medizinische Mikrobiologie, Immunologie und Hygiene
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/321687843?language=en
• 关键词: NaCl; Nuclear; Factor; Activated; Cells

Local tissue microenvironment plays a key role in shaping immune responses. We found that Na+ accumulated at the site of bacterial skin infections in humans and in mice. We used the protozoan parasite Leishmania major as a model of a skin-prone macrophage infection to test the hypothesis that skin-Na+ storage facilitates host defense. Activation of macrophages in the presence of high salt (HS) concentrations enhanced nuclear factor of activated T cells 5 (NFAT5) activation. This HS response boosted inducible nitric oxide synthase-dependent NO production and improved macrophage-driven L. major control in vitro and in vivo. Preliminary own data indicate that HS-conditions improve macrophage and granulocyte-driven antibacterial control as well. However, the mechanisms involved in this HS-enhanced antibacterial function are unknown. Next, it is unclear whether NFAT5-expression in macrophages and granulocytes is required in order to fight against bacterial infections. Here, we propose experiments that aim to uncover the antibacterial effect of HS on macrophages and granulocytes and the role of NFAT5 in this state of affair. A detailed understanding of the effects of salt and NFAT5 on antimicrobial function of phagocytes might lead to new therapeutic targets and approaches in treating bacterial infections.

局部组织微环境在形成免疫应答中起着关键作用。我们发现Na+在人类和小鼠的细菌皮肤感染部位积累。我们使用原生动物寄生虫利什曼原虫作为模型的皮肤倾向的巨噬细胞感染，以测试假设，皮肤Na+存储促进主机防御。在高盐（HS）浓度存在下巨噬细胞的活化增强了活化T细胞核因子5（NFAT 5）的活化。这种HS反应促进了诱导型一氧化氮合酶依赖的NO产生，并改善了巨噬细胞驱动的L。体外和体内主要对照。初步数据表明，HS条件也改善了巨噬细胞和粒细胞驱动的抗菌控制。然而，HS增强抗菌功能的机制尚不清楚。接下来，还不清楚巨噬细胞和粒细胞中是否需要NFAT 5表达以对抗细菌感染。在这里，我们提出了旨在揭示HS对巨噬细胞和粒细胞的抗菌作用以及NFAT 5在这种情况下的作用的实验。详细了解盐和NFAT 5对吞噬细胞抗菌功能的影响可能会为治疗细菌感染带来新的治疗靶点和方法。