title: Sodium chloride promotes pro-inflammatory macrophage polarization thereby aggravating CNS autoimmunity.
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.
authors.affiliation: Department of Neurology, University of Muenster, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hucke
authors.affiliation: Department of Neurology, University of Muenster, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Eschborn
authors.affiliation: Department of Neurology, University of Muenster, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Liebmann
authors.affiliation: Department of Neurology, University of Muenster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Herold
authors.affiliation: Institute of Immunology, University of Muenster, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Freise
authors.affiliation: Department of Neurology, University of Muenster, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Engbers
authors.affiliation: Department of Neurology, University of Muenster, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Ehling
authors.affiliation: Department of Neurology, University of Muenster, Germany; Cells in Motion, Cluster of Excellence, University of Münster, Germany.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.affiliation: Institute of Immunology, University of Muenster, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Roth
authors.affiliation: Institute of Neuropathology, University of Muenster, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Kuhlmann
authors.affiliation: Department of Neurology, University of Muenster, Germany; Cells in Motion, Cluster of Excellence, University of Münster, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.affiliation: Department of Neurology, University of Muenster, Germany. Electronic address: luisa.klotz@ukmuenster.de.
authors.forename: Luisa
authors.initials: L
authors.lastname: Klotz
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000187:drug effects; D015415:Biomarkers; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental; D006801:Humans; D016130:Immunophenotyping; D020935:MAP Kinase Signaling System; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism*; D010641:Phenotype; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*
chemical_list: D015415:Biomarkers; D017673:Sodium Chloride, Dietary
keywords: CNS autoimmunity; Dietary salt intake; Multiple sclerosis; Myeloid cells; Pro-inflammatory M1 macrophages