Cutaneous Na+ storage strengthens the antimicrobial barrier function of the skin and boosts macrophage-driven host defense
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...
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| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
March 3, 2015
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| In: |
Cell metabolism
Year: 2015, Jahrgang: 21, Heft: 3, Pages: 493-501 |
| ISSN: | 1932-7420 |
| DOI: | 10.1016/j.cmet.2015.02.003 |
| Online-Zugang: | Verlag, teilw. kostenfrei, Volltext: http://dx.doi.org/10.1016/j.cmet.2015.02.003 Verlag, teilw. kostenfrei, Volltext: http://www.sciencedirect.com/science/article/pii/S1550413115000558 
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| Verfasserangaben: | Jonathan Jantsch, Valentin Schatz, Diana Friedrich, Agnes Schröder, Christoph Kopp, Isabel Siegert, Andreas Maronna, David Wendelborn, Peter Linz, Katrina J. Binger, Matthias Gebhardt, Matthias Heinig, Patrick Neubert, Fabian Fischer, Stefan Teufel, Jean-Pierre David, Clemens Neufert, Alexander Cavallaro, Natalia Rakova, Christoph Küper, Franz-Xaver Beck, Wolfgang Neuhofer, Dominik N. Muller, Gerold Schuler, Michael Uder, Christian Bogdan, Friedrich C. Luft, and Jens Titze |
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| 520 | |a 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. | ||
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