Journal
CELL METABOLISM
Volume 21, Issue 3, Pages 493-501Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2015.02.003
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [SFB 643, DA1067/7-2]
- German Ministry for Economics and Technology [50WB1218]
- Interdisciplinary Center for Clinical Research (IZKF) Erlangen
- NIH [RO1 HL118579-01]
- American Heart Association [AHA 14SFRN20770008]
- IZKF Erlangen [A61]
- Emerging Field Initiative of the FAU
- Australian National Health and Medical Research Council [APP1037633]
- DFG
- German Center for Cardiovascular Research
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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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