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

Official URL:https://doi.org/10.1016/j.cmet.2015.02.003
PubMed:View item in PubMed
Creators Name:Jantsch, J. and Schatz, V. and Friedrich, D. and Schroeder, A. and Kopp, C. and Siegert, I. and Maronna, A. and Wendelborn, D. and Linz, P. and Binger, K.J. and Gebhardt, M. and Heinig, M. and Neubert, P. and Fischer, F. and Teufel, S. and David, J.P. and Neufert, C. and Cavallaro, A. and Rakova, N. and Kueper, C. and Beck, F.X. and Neuhofer, W. and Muller, D.N. and Schuler, G. and Uder, M. and Bogdan, C. and Luft, F.C. and Titze, J.
Journal Title:Cell Metabolism
Journal Abbreviation:Cell Metab
Volume:21
Number:3
Page Range:493-501
Date:3 March 2015
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
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.
ISSN:1550-4131
Publisher:Cell Press / Elsevier (U.S.A.)
Item Type:Article

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