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| Item Type: | Article |
|---|---|
| Title: | Cutaneous Na(+) storage strengthens the antimicrobial barrier function of the skin and boosts macrophage-driven host defense |
| Creators Name: | Jantsch, J., Schatz, V., Friedrich, D., Schröder, A., Kopp, C., Siegert, I., Maronna, A., Wendelborn, D., Linz, P., Binger, K.J., Gebhardt, M., Heinig, M., Neubert, P., Fischer, F., Teufel, S., David, J.P., Neufert, C., Cavallaro, A., Rakova, N., Küper, C., Beck, F.X., Neuhofer, W., Muller, D.N., Schuler, G., Uder, M., Bogdan, C., Luft, F.C. and Titze, J. |
| 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. |
| Keywords: | Anti-Infective Agents, Cutaneous Leishmaniasis, Enzyme Activation, Leishmania major, Macrophages, NFATC Transcription Factors, Nitric Oxide, Nitric Oxide Synthase Type II, p38 Mitogen-Activated Protein Kinases, Skin, Sodium, Animals, Mice |
| Source: | Cell Metabolism |
| ISSN: | 1550-4131 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 21 |
| Number: | 3 |
| Page Range: | 493-501 |
| Date: | 3 March 2015 |
| Additional Information: | Copyright © 2015 Elsevier Inc. All rights reserved. |
| Official Publication: | https://doi.org/10.1016/j.cmet.2015.02.003 |
| External Fulltext: | View full text on PubMed Central |
| PubMed: | View item in PubMed |
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