Salt, chloride, bleach, and innate host defense

Abstract

Salt provides 2 life-essential elements: sodium and chlorine. Chloride, the ionic form of chlorine, derived exclusively from dietary absorption and constituting the most abundant anion in the human body, plays critical roles in many vital physiologic functions, from fluid retention and secretion to osmotic maintenance and pH balance. However, an often overlooked role of chloride is its function in innate host defense against infection. Chloride serves as a substrate for the generation of the potent microbicide chlorine bleach by stimulated neutrophils and also contributes to regulation of ionic homeostasis for optimal antimicrobial activity within phagosomes. An inadequate supply of chloride to phagocytes and their phagosomes, such as in CF disease and other chloride channel disorders, severely compromises host defense against infection. We provide an overview of the roles that chloride plays in normal innate immunity, highlighting specific links between defective chloride channel function and failures in host defense.

Effects of dietary sodium on metabolites: the Dietary Approaches to Stop Hypertension (DASH)–Sodium Feeding Study

“…4-Ethylphenylsulfate is correlated with the consumption of soy products (17,18) and is elevated in the plasma of vegans compared with omnivores; a vegan diet increases concentrations of several products produced by the gut microbiota (19). Salt has known antibacterial properties (20) and has been used for medicinal purposes for centuries (21,22). Others have suggested that both diet and the microbiome mediate associations between metabolites and blood pressure (23).…”

Elementary immunology: Na+ as a regulator of immunity

“…Whether increased salt concentrations, as found in infected and inflamed skin tissue, affect the subcellular charge balance of phagosomes is as yet unknown (reviewed in [102]). In addition, it is unclear whether enhancing salt concentrations by 40 mM affects the ROS and subsequent bleach production of infected granulocytes (reviewed in [103]) and ultimately results in enhanced antimicrobial function. NaCl injection was found to promote the infiltration of neutrophils into the peritoneal cavity, which might promote local antimicrobial defense [36].…”

Environmental Effects on Reactive Oxygen Species Detection—Learning from the Phagosome

“…However the amount of HOCl also depends on the presence of chloride. The mechanism by which phagosomes acquire chloride is not clear, it probably involves different chloride channels that reach the phagosome upon fusion with intracellular organelles such as secretory vesicles and endosomes/lysosomes (75). The chloride concentration of phagosomes was estimated to 70 mM at steady state level (54).…”