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

局部组织微环境在形成免疫应答中起关键作用。我们发现Na+在人类和小鼠的细菌性皮肤感染部位积聚。我们使用原生动物寄生虫利什曼原虫作为皮肤易感巨噬细胞感染的模型来验证皮肤na +储存促进宿主防御的假设。巨噬细胞在高盐（HS）浓度下的活化增强了活化T细胞核因子5 （NFAT5）的活化。这种HS反应促进了体外和体内诱导型一氧化氮合酶依赖性NO的产生，并改善了巨噬细胞驱动的L. major控制。初步数据表明，hs条件也能改善巨噬细胞和粒细胞驱动的抗菌控制。然而，这种hs增强抗菌功能的机制尚不清楚。其次，为了对抗细菌感染，巨噬细胞和粒细胞中是否需要nfat5的表达尚不清楚。在此，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NFAT5在此状态中的作用的实验。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.