Cutaneous Na+ Storage Strengthens the Antimicrobial Barrier Function of the Skin and Boosts Macrophage-Driven Host Defense Academic Article uri icon

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.

authors

  • Jantsch, Jonathan
  • Schatz, Valentin
  • Friedrich, Diana
  • Schröder, Agnes
  • Kopp, Christoph
  • Siegert, Isabel
  • Maronna, Andreas
  • Wendelborn, David
  • Linz, Peter
  • Binger, Katrina J
  • Gebhardt, Matthias
  • Heinig, Matthias
  • Neubert, Patrick
  • Fischer, Fabian
  • Teufel, Stefan
  • David, Jean-Pierre
  • Neufert, Clemens
  • Cavallaro, Alexander
  • Rakova, Natalia
  • Küper, Christoph
  • Beck, Franz-Xaver
  • Neuhofer, Wolfgang
  • Muller, Dominik N
  • Schuler, Gerold
  • Uder, Michael
  • Bogdan, Christian
  • Luft, Friedrich C
  • Titze, Jens

publication date

  • 2015