ArticlePloS one2014
Neuro-anatomical evidence indicating indirect modulation of macrophages by vagal efferents in the intestine but not in the spleen.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
73 citing papers in PubMed, 2 syntheses or guidelines pooled it, 117 citations in OpenAlex.
- Transcutaneous auricular vagus nerve stimulation targets the brain-gut axis to treat functional dyspepsia: a scoping review of clinical evidence and mechanistic research.Frontiers in neuroscience · 2026Pooled it
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- Trial
- Effect of transcutaneous vagus nerve stimulation on muscle activity in the gastrointestinal tract (transVaGa): a prospective clinical trial.International journal of colorectal disease · 2019Trial
- Article
- Histochemical characterization of muscularis macrophage loss and disruption of a miR-93-5p-AHNAK neuro-immune axis in Hirschsprung's disease.Histochemistry and cell biology · 2026Article
- A Review of Vagus Nerve Stimulation for Disease: Comprehensive Theory and Evidence for Mechanisms of Action.Comprehensive physiology · 2026Review
- Enteric nervous system and inflammatory bowel disease.Gastroenterology report · 2026Review
- Vagus Nerve Regulation of Inflammatory Responses in Sepsis: Mechanistic Insights and Translational Applications.Journal of inflammation research · 2026Review
- Bridging the gut and mind: a narrative review of depression in Crohn's disease and emerging gut-brain axis therapies.Frontiers in neuroscience · 2026Review
- Enteric neuropathy and the vagus nerve: Therapeutic implications.Neurogastroenterology and motility · 2025Review
- Intestinal neuron-associated macrophages in health and disease.Nature immunology · 2025Review
- Transcutaneous Vagal Nerve Stimulation for Gastrointestinal Disorders.Journal of translational gastroenterology · 2025Article
- Efficacy of vagus nerve stimulation in gastrointestinal disorders: a systematic review.Gastroenterology report · 2025Review
- The molecular components of the anti-inflammatory cholinergic pathway are extrasplenic.PloS one · 2025Article
- Transcutaneous auricular vagus nerve stimulation as an innovative approach for managing perioperative gastrointestinal dysfunction: a narrative review.Frontiers in medicine · 2025Review
- Exploring the efficacy of Transcutaneous Auricular Vagus nerve stimulation (taVNS) in modulating local and systemic inflammation in experimental models of colitis.Bioelectronic medicine · 2024Article
- Atopic dermatitis and food allergy: More than sensitization.Mucosal immunology · 2024Review
- Electroacupuncture Promotes Liver Regeneration by Activating DMV Acetylcholinergic Neurons-Vagus-Macrophage Axis in 70% Partial Hepatectomy of Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- New insights into muscularis macrophages in the gut: from their origin to therapeutic targeting.Immunologic research · 2023Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundElectrical stimulation of the vagus nerve suppresses intestinal inflammation and normalizes gut motility in a mouse model of postoperative ileus. The exact anatomical interaction between the vagus nerve and the intestinal immune system remains however a matter of debate. In the present study, we provide additional evidence on the direct and indirect vagal innervation of the spleen and analyzed the anatomical evidence for neuroimmune modulation of macrophages by vagal preganglionic and enteric postganglionic nerve fibers within the intestine.
methodsDextran conjugates were used to label vagal preganglionic (motor) fibers projecting to the small intestine and spleen. Moreover, identification of the neurochemical phenotype of the vagal efferent fibers and enteric neurons was performed by immunofluorescent labeling. F4/80 antibody was used to label resident macrophages.
resultsOur anterograde tracing experiments did not reveal dextran-labeled vagal fibers or terminals in the mesenteric ganglion or spleen. Vagal efferent fibers were confined within the myenteric plexus region of the small intestine and mainly endings around nNOS, VIP and ChAT positive enteric neurons. nNOS, VIP and ChAT positive fibers were found in close proximity of intestinal resident macrophages carrying α7 nicotinic receptors. Of note, VIP receptors were found on resident macrophages located in close proximity of VIP positive nerve fibers.
conclusionIn the present study, we show that the vagus nerve does not directly interact with resident macrophages in the gut or spleen. Instead, the vagus nerve preferentially interacts with nNOS, VIP and ChAT enteric neurons located within the gut muscularis with nerve endings in close proximity of the resident macrophages.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.