Sodium chloride promotes pro-inflammatory macrophage polarization thereby aggravating CNS autoimmunity. (February 2016)

• Record Type: Journal Article
• Authors: Hucke, Stephanie; Eschborn, Melanie; Liebmann, Marie; Herold, Martin; Freise, Nicole; Engbers, Annika; Ehling, Petra; Meuth, Sven G.; Roth, Johannes; Kuhlmann, Tanja; Wiendl, Heinz; Klotz, Luisa
• Is Part Of: Journal of autoimmunity. Volume 67(2016)
• Page Start: 90
• Page End: 101
• Publication Date: 2016-02
• Subjects: Dietary salt intake -- Myeloid cells -- Pro-inflammatory M1 macrophages -- Multiple sclerosis -- CNS autoimmunity; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2015.11.001
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: The increasing incidence in Multiple Sclerosis (MS) during the last decades in industrialized countries might be linked to a change in dietary habits. Nowadays, enhanced salt content is an important characteristic of Western diet and increased dietary salt (NaCl) intake promotes pathogenic T cell responses contributing to central nervous system (CNS) autoimmunity. Given the importance of macrophage responses for CNS disease propagation, we addressed the influence of salt consumption on macrophage responses in CNS autoimmunity. We observed that EAE-diseased mice receiving a NaCl-high diet showed strongly enhanced macrophage infiltration and activation within the CNS accompanied by disease aggravation during the effector phase of EAE. NaCl treatment of macrophages elicited a strong pro-inflammatory phenotype characterized by enhanced pro-inflammatory cytokine production, increased expression of immune-stimulatory molecules, and an antigen-independent boost of T cell proliferation. This NaCl-induced pro-inflammatory macrophage phenotype was accompanied by increased activation of NF-kB and MAPK signaling pathways. The pathogenic relevance of NaCl-conditioned macrophages is illustrated by the finding that transfer into EAE-diseased animals resulted in significant disease aggravation compared to untreated macrophages. Importantly, also in human monocytes, NaCl promoted a pro-inflammatory phenotype that enhanced human T cell proliferation. Taken together, high dietary salt intake promotes pro-inflammatory macrophages that aggravate CNS autoimmunity. Together with other studies, these results underline the need to further determine the relevance of increased dietary salt intake for MS disease severity. Highlights: Dietary salt content changes were recently linked to increased MS disease incidence. Enhanced dietary salt intake aggravates macrophage responses during EAE. Increased salt levels induce pro-inflammatory phenotype in human/murine macrophages. Salt-induced pro-inflammatory macrophages aggravate ongoing EAE. Study further underlines need to determine dietary influence on MS disease activity.