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

Tools

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

Repository Staff Only: item control page