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

Binger KJ, Gebhardt M, Heinig M, Rintisch C, Schröder A, Neuhofer W, Hilgers KF, Manzel A, Schwartz C, Kleinewietfeld M, Voelkl J, Schatz V, Linker R, Lang F, Vöhringer D, Wright MD, Hubner N, Dechend R, Jantsch J, Titze J, Mueller DN (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Journal of Clinical Investigation American Society for Clinical Investigation

Book Volume: 125

Pages Range: 4223-38

Journal Issue: 11

DOI: 10.1172/JCI80919

Abstract

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.

Authors with CRIS profile

Agnes Schröder Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung Karl Friedrich Hilgers Professur für Innere Medizin (Hochdruckforschung) Christian Schwartz Department of Infection Biology Ralf Linker
David Vöhringer Professur für Infektionsabwehr und Toleranz Jens Titze Professur für Elektrolyt- und Kreislaufforschung

Involved external institutions

Experimental and Clinical Research Center (ECRC) DE Germany (DE) Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE) Technische Universität Dresden DE Germany (DE) Eberhard Karls Universität Tübingen DE Germany (DE) Universitätsklinikum Regensburg DE Germany (DE) Monash University AU Australia (AU)

How to cite

APA:

Binger, K.J., Gebhardt, M., Heinig, M., Rintisch, C., Schröder, A., Neuhofer, W.,... Mueller, D.N. (2015). High salt reduces the activation of IL-4- and IL-13-stimulated macrophages. Journal of Clinical Investigation, 125(11), 4223-38. https://dx.doi.org/10.1172/JCI80919

MLA:

Binger, Katrina J., et al. "High salt reduces the activation of IL-4- and IL-13-stimulated macrophages." Journal of Clinical Investigation 125.11 (2015): 4223-38.

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