ArticlePLoS pathogens2019
T-cell derived acetylcholine aids host defenses during enteric bacterial infection with Citrobacter rodentium.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 62 citations in OpenAlex.
- Neuro-immune interactions in tumors, immune-related disorders, and infections.Signal transduction and targeted therapy · 2026Review
- Host-microbiome interactions and enteric pathogen infections-from early-life to long-term impacts on gut-brain communication.Journal of applied microbiology · 2026Review
- Vagus nerve stimulation limits colonic inflammation through distinct neuroimmune circuitry shaped by inflammatory history.bioRxiv : the preprint server for biology · 2026Article
- Neuro-immune interactions in gastrointestinal oncology: Mechanisms, challenges, and therapeutic potential.Innovation (Cambridge (Mass.)) · 2026Review
- Nociceptor α7nAChR activation blunts neuronal HMGB1 release and attenuates inflammation and nociceptive behavior.Molecular medicine (Cambridge, Mass.) · 2025Article
- The sympathetic nervous system enhances host immune responses to enteric bacterial pathogens in mice.Brain, behavior, and immunity · 2025Article
- Bidirectional regulation of the brain-gut-microbiota axis following traumatic brain injury.Neural regeneration research · 2025Article
- Citrobacter rodentium infection activates colonic lamina propria group 2 innate lymphoid cells.PLoS pathogens · 2025Article
- Inhibition of acute lung inflammation by a neuroimmune circuit induced by vagal nerve stimulation.Science advances · 2025Article
- B cells modulate lung antiviral inflammatory responses via the neurotransmitter acetylcholine.Nature immunology · 2025Article
- Neuroimmune interactions: The bridge between inflammatory bowel disease and the gut microbiota.Clinical and translational medicine · 2025Review
- Goblet cells: guardians of gut immunity and their role in gastrointestinal diseases.eGastroenterology · 2024Article
- Cholinergic macrophages promote the resolution of peritoneal inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- 2023 Workshop: Neuroimmune Crosstalk in the Gut - Impact on Local, Autonomic and Gut-Brain Function.Gastroenterology · 2024Article
- T cells at the interface of neuroimmune communication.The Journal of allergy and clinical immunology · 2024Review
- Bridging the Mind and Gut: Uncovering the Intricacies of Neurotransmitters, Neuropeptides, and their Influence on Neuropsychiatric Disorders.Central nervous system agents in medicinal chemistry · 2024Review
- TRPV1 controls innate immunity during Citrobacter rodentium enteric infection.PLoS pathogens · 2023Article
- The role of cellular and molecular neuroimmune crosstalk in gut immunity.Cellular & molecular immunology · 2023Review
- Cholinergic Polarization of Human Macrophages.International journal of molecular sciences · 2023Review
- Impact of Donepezil Supplementation on Alzheimer's Disease-like Pathology and Gut Microbiome in APP/PS1 Mice.Microorganisms · 2023Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
The regulation of mucosal immune function is critical to host protection from enteric pathogens but is incompletely understood. The nervous system and the neurotransmitter acetylcholine play an integral part in host defense against enteric bacterial pathogens. Here we report that acetylcholine producing-T-cells, as a non-neuronal source of ACh, were recruited to the colon during infection with the mouse pathogen Citrobacter rodentium. These ChAT+ T-cells did not exclusively belong to one Th subset and were able to produce IFNγ, IL-17A and IL-22. To interrogate the possible protective effect of acetylcholine released from these cells during enteric infection, T-cells were rendered deficient in their ability to produce acetylcholine through a conditional gene knockout approach. Significantly increased C. rodentium burden was observed in the colon from conditional KO (cKO) compared to WT mice at 10 days post-infection. This increased bacterial burden in cKO mice was associated with increased expression of the cytokines IL-1β, IL-6, and TNFα, but without significant changes in T-cell and ILC associated IL-17A, IL-22, and IFNγ, or epithelial expression of antimicrobial peptides, compared to WT mice. Despite the increased expression of pro-inflammatory cytokines during C. rodentium infection, inducible nitric oxide synthase (Nos2) expression was significantly reduced in intestinal epithelial cells of ChAT T-cell cKO mice 10 days post-infection. Additionally, a cholinergic agonist enhanced IFNγ-induced Nos2 expression in intestinal epithelial cell in vitro. These findings demonstrated that acetylcholine, produced by specialized T-cells that are recruited during C. rodentium infection, are a key mediator in host-microbe interactions and mucosal defenses.
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