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Too much Salt in Food can push the Immune System out of Equilibrium

Too much salt in food can influence the immune system. In a study published recently in the Journal of Clinical Investigation*, Dr. Katrina Binger, Matthias Gebhardt, and Professor Dominik Müller from the Experimental Clinical Research Center (ECRC) of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) and Charité – Universitätsmedizin Berlin establish that increased salt consumption by rodents leads to delayed healing of their wounds because too much salt pushes the immune system out of equilibrium. At the same time, they were successful in explaining the mechanism causing this imbalance.

Too much salt in food is unhealthy. Physicians and scientists studying nutrition agree on this and warn of consuming too much salt. It is well known that table salt (sodium chloride) can drive blood pressure upwards. It may also be partly responsible for cardiovascular disease, chronic diseases, autoimmune diseases, as well as cancer. “However, we still don’t understand the underlying mechanisms causing this response,” says Professor Müller. “And we don’t know how much salt is too much, that is, how much salt we can eat without compromising our health.”

Genetics play a large part in the diseases mentioned, yet the sharp rise in inflammatory diseases as well as autoimmune diseases – in which the immune system mistakenly destroys endogenous structures – suggests that environmental factors also contribute to these diseases in an important way. “Western” eating habits characterized by high fat and salt levels have recently come under particular suspicion.

It has become clear the last few years that excessive salt in food also has effects on the immune system, and in diverse ways. In their study recently published in the Journal of Clinical Investigation, Dr. Binger, Matthias Gebhardt, and Professor Müller furnish proof that too much salt in food weakens a specific group of scavenger cells (macrophages) in the immune system. Macrophages are the first responders to infection and are important in warding off a variety of pathogens. One of whose jobs is to combat inflammation in the body. A particular type of these cells, known as type 2 macrophages, also play a critical role in repairing wounds and combating too much inflammation. In rodents fed a high-salt diet, wound healing was delayed – in part of course because of the salt-related weakening of these particular scavenger cells, as the scientists surmised.

A research team headed by Professor Jens Titze, Vanderbilt University (Nashville, Tennessee USA), together with the Berlin researchers recently discovered a new salt reservoir in the body Excess salt is deposited in the interstitium of tissues like skin rather than in the blood, for example, since the kidneys continuously regulate the salt content there. These new insights enabled the three MDC scientists to also explain the mechanism of how table salt weakens the activity of the macrophages.

A group of researchers including Professor Müller had first discovered a different effect of salt on the immune system in 2013. In a study published in Nature, they had proven that elevated salt consumption promotes the development of autoimmune diseases. The reason: too much salt leads to a sharp rise of a group of aggressive immune cells (Th17 helper cells). These T helper cells that produce the messenger compound interleukin 17 (hence their name) are partly to blame for the immune system running wild, attacking and damaging its own organism.

Professor Titze, Professor Müller, and Matthias Gebhardt jointly with other researchers produced the first evidence early this year that high salt consumption in both rodents and patients puts the immune system in high gear and finishes off bacterial infections in the skin (Cell Metabolism). The reason: salt gets deposited in the skin and, in the event of a bacterial skin infection, activates type 1 macrophages that release increased bactericides. In this situation however, Professor Müller warns against eating too much salt: “The risks outweigh the benefits.” Moreover: “These seemingly contradictory findings indicate macrophages can adapt in different ways to an environment that itself changes with elevated salt volumes in the body.

*High salt reduces the activation of IL-4+IL-13 stimulated 1 macrophages

Katrina J. Binger1,2,12, 13, Matthias Gebhardt1,2,12, Matthias Heinig2, Carola Rintisch2, Agnes Schroeder3, Wolfgang Neuhofer4, Karl Hilgers3, Arndt Manzel3, Christian Schwartz3, Markus Kleinewietfeld5,6, Jakob Voelkl7, Valentin Schatz8, Ralf A. Linker3, Florian Lang7, David Voehringer3, Mark D. Wright9, Norbert Hübner2, Ralf Dechend1,10, Jonathan Jantsch8, Jens Titze3,11, Dominik N. Müller1,2,13

1Experimental and Clinical Research Center, an institutional cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine, Berlin, 13125, Germany

2Max Delbrück Center for Molecular Medicine, Berlin, 13125, Germany; German Centre for Cardiovascular Research Partner Site Berlin, Germany

3University Hospital Erlangen at the Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Erlangen, 91054, Germany

4Ludwig-Maximillian-University of Munich, Munich, 80539, Germany

5Translational Immunology, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, 01307, Germany

6DFG-Center for Regenerative Therapies Dresden (CRTD), Dresden, 01307, Germany

7University of Tübingen, Tübingen, 72076, Germany

8University Hospital Regensburg, Regensburg, 93053, Germany

9Department of Immunology, Monash University, Melbourne, 3004, Australia

10HELIOS-Klinikum Berlin, Berlin, 13125, Germany

11Vanderbilt University, Nashville, TN, 37235, USA

12equal contribution

13correspondance to:

Dominik N. Muller, Tel: +40 (0)30 450-540 286. E-mail: dominik.mueller@mdc.de

Katrina J. Binger Tel: +61 (0)3 8532 1111. E-mail: katrinabinger@gmail.com

Contact:
Barbara Bachtler
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Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC)
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