TY - JOUR
T1 - High salt reduces the activation of IL-4- and IL-13-stimulated macrophages
AU - Binger, Katrina
AU - Gebhardt, Matthias
AU - Heinig, Matthias
AU - Rintisch, Carola
AU - Schroeder, Agnes
AU - Neuhofer, Wolfgang
AU - Hilgers, Karl Friedrich
AU - Manzel, Arndt
AU - Schwartz, Christian
AU - Kleinewietfeld, Markus
AU - Voelkl, Jakob G J
AU - Schatz, Valentin
AU - Linker, Ralf A
AU - Lang, Florian
AU - Voehringer, David W
AU - Wright, Mark Dexter
AU - Hubner, Norbert
AU - Dechend, Ralf
AU - Jantsch, Jonathan
AU - Titze, Jens Marc
AU - Muller, Dominik N
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - https://www.jci.org/articles/view/80919/pdf
U2 - 10.1172/JCI80919
DO - 10.1172/JCI80919
M3 - Article
VL - 125
SP - 4223
EP - 4238
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 11
ER -