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Updated in 1/17/2017 5:40:05 PM      Viewed: 1030 times      (Journal Article)
Cell metabolism 21 (3): 493-501 (2015)

Cutaneous Na+ storage strengthens the antimicrobial barrier function of the skin and boosts macrophage-driven host defense.

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 , Jens Titze
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.
DOI: 10.1016/j.cmet.2015.02.003      ISSN: 1550-4131