ArticleCell metabolism2015
Cutaneous Na+ storage strengthens the antimicrobial barrier function of the skin and boosts macrophage-driven host defense.
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Article in Cell metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 200 papers.
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200citing papers in PubMed
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200 citing papers in PubMed, 317 citations in OpenAlex.
- Effects of altered salt intake and diet on cytokines in humans: A 20-week randomized cross-over intervention study.European journal of immunology · 2023Trial
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- A pilot, open labelled, randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold.Scientific reports · 2019Trial
- Increased salt consumption induces body water conservation and decreases fluid intake.The Journal of clinical investigation · 2017Trial
- Salt and chronic kidney disease.Nature reviews. Nephrology · 2026Review
- Estimation of skin sodium content viaMagma (New York, N.Y.) · 2026Article
- High-salt diet in macrophage-associated metabolic disorders: Mechanisms and therapeutic implications.Chinese medical journal · 2026Review
- Nasal Irrigation in Children: From Pathophysiological Rationale to Clinical Practice.Children (Basel, Switzerland) · 2026Review
- Transcriptomic Analysis Reveals Novel Mechanisms Underlying Neutrophil Activation Induced by High Salt.International journal of molecular sciences · 2026Article
- High-salt diet induces immune-independent re-differentiation, metabolic shut down and cell cycle arrest of melanoma.Cell death & disease · 2025Article
- Blood pressure reduction and anti-inflammatory macrophage augmentation attenuate uterine immune dysregulation and inflammation in mice with salt-sensitive hypertension.Clinical science (London, England : 1979) · 2025Article
- Epigenetic landscape of Leishmania-host interactions.Epigenomics · 2025Review
- Nasal Irrigations: A 360-Degree View in Clinical Practice.Medicina (Kaunas, Lithuania) · 2025Review
- The Role of Nrf2 in the Regulation of Periodontitis, Peri-implantitis, Dentin Infection, and Apical Periodontitis.Biological procedures online · 2025Review
- Dietary salt, vascular dysfunction, and cognitive impairment.Cardiovascular research · 2025Review
- A comprehensive review on cardiovascular disorders development due to salt intake: an emphasis on policy implementation.Health research policy and systems · 2025Review
- Sodium MRI of the skin using a surface coil to investigate and reduce signal loss and bias.Magnetic resonance in medicine · 2025Article
- Metal Ion Signaling in Biomedicine.Chemical reviews · 2025Review
- Sodium-Directed Crosstalk Between Immune Cells and Lymphatic Vessels.Current hypertension reports · 2025Review
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
140 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors at 8 institutions in 2 countries.
Jonathan JantschMicrobiology Institute - Clinical Microbiology, Immunology and Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany; Institute of Clinical Microbiology and Hygiene, Universitätsklinikum Regensburg and Universität Regensburg, Regensburg, Germany. Electronic address: Jonathan.Jantsch@ukr.de.
Valentin SchatzMicrobiology Institute - Clinical Microbiology, Immunology and Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany; Institute of Clinical Microbiology and Hygiene, Universitätsklinikum Regensburg and Universität Regensburg, Regensburg, Germany.
Diana FriedrichMicrobiology Institute - Clinical Microbiology, Immunology and Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany; Interdisciplinary Center for Clinical Research and Department of Nephrology and Hypertension, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Germany.
Agnes SchröderInterdisciplinary Center for Clinical Research and Department of Nephrology and Hypertension, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Germany.
Christoph KoppInterdisciplinary Center for Clinical Research and Department of Nephrology and Hypertension, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Germany.
Isabel SiegertMicrobiology Institute - Clinical Microbiology, Immunology and Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.
Andreas MaronnaDepartment of Dermatology, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Germany.
David WendelbornMicrobiology Institute - Clinical Microbiology, Immunology and Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany; Interdisciplinary Center for Clinical Research and Department of Nephrology and Hypertension, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Germany.
Peter LinzInterdisciplinary Center for Clinical Research and Department of Nephrology and Hypertension, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Germany.
Katrina J BingerExperimental and Clinical Research Center (ECRC), an institutional cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin, Germany; Max-Delbrück Center for Molecular Medicine, Berlin Germany.
Matthias GebhardtExperimental and Clinical Research Center (ECRC), an institutional cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin, Germany; Max-Delbrück Center for Molecular Medicine, Berlin Germany.
Matthias HeinigMax-Delbrück Center for Molecular Medicine, Berlin Germany; Department of Computational Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Patrick NeubertInterdisciplinary Center for Clinical Research and Department of Nephrology and Hypertension, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Germany.
Fabian FischerMicrobiology Institute - Clinical Microbiology, Immunology and Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.
Stefan TeufelDepartment of Internal Medicine 3, Rheumatology and Immunology, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Germany; Institute for Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Jean-Pierre DavidDepartment of Internal Medicine 3, Rheumatology and Immunology, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Germany; Institute for Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Clemens NeufertDepartment of Internal Medicine 1, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg.
Alexander CavallaroDepartment of Radiology, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Germany.
Natalia RakovaExperimental and Clinical Research Center (ECRC), an institutional cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin, Germany.
Christoph KüperDepartment of Physiology, Ludwig-Maximilians-Universität München, Munich, Germany.
Franz-Xaver BeckDepartment of Physiology, Ludwig-Maximilians-Universität München, Munich, Germany.
Wolfgang NeuhoferV. Medical Clinic, University Hospital Mannheim, Mannheim, Germany.
Dominik N MullerExperimental and Clinical Research Center (ECRC), an institutional cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin, Germany; Max-Delbrück Center for Molecular Medicine, Berlin Germany.
Gerold SchulerDepartment of Dermatology, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Germany.
Michael UderDepartment of Radiology, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Germany.
Christian BogdanMicrobiology Institute - Clinical Microbiology, Immunology and Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany.
Friedrich C LuftExperimental and Clinical Research Center (ECRC), an institutional cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin, Germany; Divison of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Jens TitzeInterdisciplinary Center for Clinical Research and Department of Nephrology and Hypertension, Universitätsklinikum Erlangen and Friedrich-Alexander Universität (FAU) Erlangen-Nürnberg, Germany; Divison of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Universitätsklinikum Erlangen · DEMax Delbrück Center · DELudwig-Maximilians-Universität München · DEVanderbilt University · USCharité - Universitätsmedizin Berlin · DEMax Planck Institute for Molecular Genetics · DEUniversity Hospital Heidelberg · DEUniversity of Regensburg · DE
Funding
Lymphatic Regulation of Skin Electrolyte Metabolism and Blood PressureR01HL118579 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI TITZE, JENS MARC · 2013 to 2017
$1.9MNHLBI NIH HHS R01 HL118579NHLBI NIH HHS R01 HL118579-01
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.
Indexed as
AnimalsAnti-Infective AgentsEnzyme ActivationHumansLeishmania majorLeishmaniasis, CutaneousMacrophagesMiceNFATC Transcription FactorsNitric OxideNitric Oxide Synthase Type IIp38 Mitogen-Activated Protein KinasesSkinSodiumAnti-Infective AgentsNFATC Transcription FactorsNitric OxideNitric Oxide Synthase Type IIp38 Mitogen-Activated Protein KinasesSodium
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