Cutaneous Na(+) storage strengthens the antimicrobial barrier function of the skin and boosts macrophage-driven host defense
Authors
- J. Jantsch
- V. Schatz
- D. Friedrich
- A. Schröder
- C. Kopp
- I. Siegert
- A. Maronna
- D. Wendelborn
- P. Linz
- K.J. Binger
- M. Gebhardt
- M. Heinig
- P. Neubert
- F. Fischer
- S. Teufel
- J.P. David
- C. Neufert
- A. Cavallaro
- N. Rakova
- C. Küper
- F.X. Beck
- W. Neuhofer
- D.N. Muller
- G. Schuler
- M. Uder
- C. Bogdan
- F.C. Luft
- J. Titze
Journal
- Cell Metabolism
Citation
- Cell Metab 21 (3): 493-501
Abstract
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.