[PDF][PDF] Cutaneous Na+ storage strengthens the antimicrobial barrier function of the skin and boosts macrophage-driven host defense

J Jantsch, V Schatz, D Friedrich, A Schröder, C Kopp… - Cell metabolism, 2015 - cell.com
J Jantsch, V Schatz, D Friedrich, A Schröder, C Kopp, I Siegert, A Maronna, D Wendelborn…
Cell metabolism, 2015cell.com
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 …
Summary
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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