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

局部组织微环境对免疫反应的形成起着关键作用。我们发现，Na+在人类和小鼠的皮肤细菌感染部位积累。我们使用原生动物寄生虫利什曼原虫作为皮肤易受巨噬细胞感染的模型，以验证皮肤钠离子储存有助于宿主防御的假设。巨噬细胞在高盐(HS)存在下的激活增强了激活的T细胞的核因子5(NFAT5)的激活。这种HS反应促进了诱导型一氧化氮合酶依赖的NO的产生，并在体外和体内改善了巨噬细胞驱动的主要对照。初步的自身数据表明，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。其次，目前尚不清楚是否需要在巨噬细胞和粒细胞中表达NFAT5以对抗细菌感染。在这里，我们提出了一些实验，旨在揭示HS对巨噬细胞和粒细胞的抗菌作用，以及NFAT5在这种情况下的作用。详细了解盐和NFAT5对吞噬细胞抗菌功能的影响，可能会为治疗细菌感染提供新的治疗靶点和方法。

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.