Journal Article

High salt reduces the activation of IL-4– and IL-13–stimulated macrophages

Manzel, Arndt, Schroeder, Agnes, Hilgers, Karl, Binger, Katrina J., Kleinewietfeld, Markus, Gebhardt, Matthias, Wright, Mark D., Voehringer, David, Dechend, Ralf, Schwartz, Christian, Lang, Florian, Linker, Ralf A., Schatz, Valentin, Hubner, Norbert, Jantsch, Jonathan, Titze, Jens, Müller, Dominik N., Neuhofer, Wolfgang, Voelkl, Jakob, Rintisch, Carola, Heinig, Matthias

2015

Overview

A high intake of dietary salt (NaCl) has been implicated in the development of hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that salt has a proinflammatory effect and boosts the activation of Th17 cells and the activation of classical, LPS-induced macrophages (M1). Here, we examined how the activation of alternative (M2) macrophages is affected by salt. In stark contrast to Th17 cells and M1 macrophages, high salt blunted the alternative activation of BM-derived mouse macrophages stimulated with IL-4 and IL-13, M(IL-4+IL-13) macrophages. Salt-induced reduction of M(IL-4+IL-13) activation was not associated with increased polarization toward a proinflammatory M1 phenotype. In vitro, high salt decreased the ability of M(IL-4+IL-13) macrophages to suppress effector T cell proliferation. Moreover, mice fed a high salt diet exhibited reduced M2 activation following chitin injection and delayed wound healing compared with control animals. We further identified a high salt-induced reduction in glycolysis and mitochondrial metabolic output, coupled with blunted AKT and mTOR signaling, which indicates a mechanism by which NaCl inhibits full M2 macrophage activation. Collectively, this study provides evidence that high salt reduces noninflammatory innate immune cell activation and may thus lead to an overall imbalance in immune homeostasis.

• Publisher: American Society for Clinical Investigation
• Subject: Acquisitions & mergers / Animals / Biological control systems / Biomedical research / Bone Marrow Cells - drug effects / Cells, Cultured / Chitin - toxicity / Cytokines / Experiments / Gene expression / Gene Expression Regulation - drug effects / Glycolysis - drug effects / Health aspects / Histone Code - drug effects / Hypertension / Immune response / Immunity, Innate - drug effects / Inflammation / Interleukin-13 - pharmacology / Interleukin-4 - pharmacology / Kinases / Macrophage Activation - drug effects / Macrophages / Macrophages - classification / Macrophages - drug effects / Macrophages - immunology / Male / Medical research / Medicine, Experimental / Metabolism / Mice / Mice, Inbred C57BL / Mice, Transgenic / Mitochondria - drug effects / Observations / Oxidative Phosphorylation - drug effects / Properties / Proto-Oncogene Proteins c-akt - genetics / Proto-Oncogene Proteins c-akt - physiology / Random Allocation / Salt / Signal Transduction - drug effects / Sodium / Sodium Chloride - pharmacology / Sodium Chloride, Dietary - pharmacology / Sodium Chloride, Dietary - toxicity / TOR Serine-Threonine Kinases - physiology / Wound healing / Wound Healing - drug effects