Cutaneous na(+) storage strengthens the antimicrobial barrier function of the skin and boosts macrophage-driven host defense
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Cutaneous na(+) storage strengthens the antimicrobial barrier function of the skin and boosts macrophage-driven host defense. / Jantsch, Jonathan; Schatz, Valentin; Friedrich, Diana; Schröder, Agnes; Kopp, Christoph; Siegert, Isabel; Maronna, Andreas; Wendelborn, David; Linz, Peter; Binger, Katrina J; Gebhardt, Matthias; Heinig, Matthias; Neubert, Patrick; Fischer, Fabian; Teufel, Stefan; David, Jean-Pierre; Neufert, Clemens; Cavallaro, Alexander; Rakova, Natalia; Küper, Christoph; Beck, Franz-Xaver; Neuhofer, Wolfgang; Muller, Dominik N; Schuler, Gerold; Uder, Michael; Bogdan, Christian; Luft, Friedrich C; Titze, Jens.
in: CELL METAB, Jahrgang 21, Nr. 3, 03.03.2015, S. 493-501.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Cutaneous na(+) storage strengthens the antimicrobial barrier function of the skin and boosts macrophage-driven host defense
AU - Jantsch, Jonathan
AU - Schatz, Valentin
AU - Friedrich, Diana
AU - Schröder, Agnes
AU - Kopp, Christoph
AU - Siegert, Isabel
AU - Maronna, Andreas
AU - Wendelborn, David
AU - Linz, Peter
AU - Binger, Katrina J
AU - Gebhardt, Matthias
AU - Heinig, Matthias
AU - Neubert, Patrick
AU - Fischer, Fabian
AU - Teufel, Stefan
AU - David, Jean-Pierre
AU - Neufert, Clemens
AU - Cavallaro, Alexander
AU - Rakova, Natalia
AU - Küper, Christoph
AU - Beck, Franz-Xaver
AU - Neuhofer, Wolfgang
AU - Muller, Dominik N
AU - Schuler, Gerold
AU - Uder, Michael
AU - Bogdan, Christian
AU - Luft, Friedrich C
AU - Titze, Jens
N1 - Copyright © 2015 Elsevier Inc. All rights reserved.
PY - 2015/3/3
Y1 - 2015/3/3
N2 - Immune cells regulate a hypertonic microenvironment in the skin; however, the biological advantage of increased skin Na(+) concentrations is unknown. We found that Na(+) accumulated at the site of bacterial skin infections in humans and in mice. We used the protozoan parasite Leishmania major as a model of skin-prone macrophage infection to test the hypothesis that skin-Na(+) storage facilitates antimicrobial host defense. Activation of macrophages in the presence of high NaCl concentrations modified epigenetic markers and enhanced p38 mitogen-activated protein kinase (p38/MAPK)-dependent nuclear factor of activated T cells 5 (NFAT5) activation. This high-salt response resulted in elevated type-2 nitric oxide synthase (Nos2)-dependent NO production and improved Leishmania major control. Finally, we found that increasing Na(+) content in the skin by a high-salt diet boosted activation of macrophages in a Nfat5-dependent manner and promoted cutaneous antimicrobial defense. We suggest that the hypertonic microenvironment could serve as a barrier to infection.
AB - Immune cells regulate a hypertonic microenvironment in the skin; however, the biological advantage of increased skin Na(+) concentrations is unknown. We found that Na(+) accumulated at the site of bacterial skin infections in humans and in mice. We used the protozoan parasite Leishmania major as a model of skin-prone macrophage infection to test the hypothesis that skin-Na(+) storage facilitates antimicrobial host defense. Activation of macrophages in the presence of high NaCl concentrations modified epigenetic markers and enhanced p38 mitogen-activated protein kinase (p38/MAPK)-dependent nuclear factor of activated T cells 5 (NFAT5) activation. This high-salt response resulted in elevated type-2 nitric oxide synthase (Nos2)-dependent NO production and improved Leishmania major control. Finally, we found that increasing Na(+) content in the skin by a high-salt diet boosted activation of macrophages in a Nfat5-dependent manner and promoted cutaneous antimicrobial defense. We suggest that the hypertonic microenvironment could serve as a barrier to infection.
U2 - 10.1016/j.cmet.2015.02.003
DO - 10.1016/j.cmet.2015.02.003
M3 - SCORING: Journal article
C2 - 25738463
VL - 21
SP - 493
EP - 501
JO - CELL METAB
JF - CELL METAB
SN - 1550-4131
IS - 3
ER -