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

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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.