Conventional wisdom holds that consuming too much sodium chloride is bad for you. High-salt diets have been linked to high blood pressure, cardiovascular disease, and even autoimmune disorders. But a new study shows that dietary salt could also have immune-boosting effects. Researchers report that high levels of salt in skin help mice fight off bacteria and that humans may also stockpile salt at infection sites.
“The idea that salt storage might have evolved for host defense is very exciting,” says Gwen Randolph, an immunologist at Washington University in St. Louis who was not involved in the study. “It’s almost so new that it’s hard to swallow. I think it will take some time for the immunology community to allow this concept to take hold.”
Scientists only recently learned that the connective tissue of skin can serve as a reservoir for sodium ions when we consume large amounts of salt. When Jens Titze, a clinical pharmacologist at the Vanderbilt University School of Medicine in Nashville and the study’s principle author, was studying dietary salt intake in mice, he noticed that even mice on low-salt diets had unusually high salt concentrations in wounded skin. Titze and his colleagues realized that immune cells arriving in wounded skin to fight infections were entering a salty microenvironment. They hypothesized that the body was shuffling salt to infected skin to protect against invaders. In other words, “we are salting our cells in order to protect ourselves,” says Jonathan Jantsch, a microbiologist at the University of Regensburg in Germany and first author on the study, which appears in the current issue of Cell Metabolism.
To find out if all that extra sodium chloride was harming or helping immunity, the researchers turned to macrophages, an immune cell that engulfs and digests invading pathogens. Activated macrophages kill off invaders by releasing microbe-slaying molecules called reactive oxygen species, and the team thought high salt concentrations might trigger the immune cells to produce these compounds. The team cultured macrophages from mice and sprinkled salt into the nutrient bath until the cells were growing in a sodium chloride concentration equivalent to what they’d seen in the rodents’ infected skin. Salt increased the microbe-killing capacity of the immune cells, the team reports; the macrophages exposed to high levels of sodium chloride released significantly more microbicidal molecules than those that grew in a culture medium without salt. Next, the team infected macrophages with the common pathogens Escherichia coli or Leishmania major. After 24 hours, the E. coli load in macrophages exposed to high sodium chloride levels was less than half of that of macrophages cultured without salt, and L. major infections were down as well.
To test whether increased salt intake enhances immune defense in living mice, the researchers fed one group of mice a high-salt diet and the other group a low-salt diet for 2 weeks, then infected the skin on the rodents’ footpads with L. major. For the following 20 days, both groups of mice showed significant swelling in their footpads as the infection took hold, regardless of their diet. After that period, however, mice on the high-salt diet showed improved healing with fewer foot lesions and a lower parasite load than the group eating low-salt food.
“[The experiments] demonstrate that extremes of salt intake result in additional salt accumulation in infected skin and boost immune defense experimentally,” Jantsch says.
In humans, the group found evidence that salt accumulation may be localized to sites of infection. Using a new MRI technique that measures sodium in skin, the team found unusually high levels of salt accumulation in bacterial skin infections of people, whether they consumed a high-salt diet.
Taken together, the group’s findings indicate that both mice and humans may be benefiting from a salt-driven boost in immune defense. But don’t start loading more salt on your fries just yet. “The one thing you don’t want to take away from this study is that it authorizes you to eat more salt to enhance immunity,” Randolph says. A high-salt diet may have been a useful way to fight infections in our ancestors, before antibiotics existed or we lived long enough to develop cardiovascular diseases, but today, the detrimental effects of a high-salt diet outweigh any potential immunological benefits, according to Jantsch. Increasing salt concentration in infected skin from outside the body—by loading tissues with salty intravenous fluids, wound gels, or dressings—may be a more realistic potential application of the findings, he says.
Additional research is needed before such treatments are feasible, but the findings “do raise the possibility that this relatively simple mechanism might be able to enhance or promote immunity,” says Thomas Coffman, a nephrologist at Duke University Medical Center in Durham, North Carolina. “It is very provocative from that standpoint.”