Search

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.

In Section 3 of his paper (N. Gisin, Phys. Lett. A 210 (1996) 151), Gisin argues that a ``careless application of generalized quantum measurements can violate Bell's inequality even for mixtures of product states.'' However, the observed violation of the CHSH inequality is not in fact due to the application of generalized quantum measurements, but rather to a misapplication of the inequality itself -- to conditional expectations in which the conditioning depends upon the measurements under consideration.