{
  "abstract": "Background: Infection with enteric bacterial pathogens continues to cause significant morbidity and mortality throughout the world. Effective control of these infections requires coordinated immune responses that are shaped in part by bidirectional communication between the nervous and immune systems. Sensory neurons are now well appreciated to detect inflammatory or microbial stimuli in numerous organ systems, including the gastrointestinal (GI) tract, and for eliciting the recruitment or activation of specific immune cells. Central to the host protective effect of these neuroimmune circuits is the localized release of neurotransmitters that activate substance P (SP) receptor signaling. However, the precise contribution of sensory neuropeptides encoded by the Tac1 gene, such as SP, in the host response to enteric infection remains incompletely understood. Methods: The role of the Tac1-encoded sensory neurotransmitters in the host response to Citrobacter rodentium was assessed using Tac1-/- and wildtype (WT) mice. Infection and inflammation were determined by bacterial enumeration, histopathology, qPCR, and flow cytometry. Results: Tac1-/- mice had significantly reduced pathogen shedding and colonic bacterial burden, accompanied by decreased expression of inflammatory cytokines and chemokines compared to WT controls. In accordance with reduced chemokine production, we observed reduced colonic recruitment of neutrophils, monocytes, and IFNγ- and IL-17A-producing T-cells in Tac1-/- compared with WT mice. This reduced immune response was associated with markedly reduced colonic histopathology. Conclusions: Sensory neuropeptides encoded by Tac1 regulate key aspects of the immune response to enteric bacterial infection and may serve as unique targets in the treatment of enteric disease. Author summary: Intestinal infections remain a major cause of illness and death worldwide. Nerves that detect tissue injury, microbes, or microbial products can shape the immune response by releasing chemical messengers. The Tac1 gene encodes several of these messengers, including substance P, but their role during intestinal bacterial infection remains unclear. To address this, we infected mice lacking the Tac1 gene with the mouse-adapted bacterial pathogen Citrobacter rodentium. Mice deficient in Tac1 had fewer bacteria than wild-type mice and exhibited reduced inflammation. This included reduced recruitment of neutrophils, monocytes, and T cells to the colon. Colonic tissue damage was also reduced. Our findings show that Tac1-derived neuropeptides do not simply enhance antibacterial immunity but can amplify inflammation without improving pathogen control. These results highlight that many signals contribute to the host immune response and that selective targeting of this pathway could provide a new approach to limiting disease during infection.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Anatomy, Physiology & Cell Biology. School of Veterinary Medicine, University of California Davis, Davis, California.United States of America"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Elliot Lloyd"
    },
    {
      "name": "Michael Cremin"
    },
    {
      "name": "Emmy Tay"
    },
    {
      "name": "Kristina Sanchez"
    },
    {
      "name": "Jungjae Park"
    },
    {
      "name": "YuanYuan Lei"
    },
    {
      "name": "Melanie G. Gareau"
    },
    {
      "name": "Colin Reardon"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7bz2v5czjma59.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.ppat.1014587",
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  "id": "7bz2v5czjma59",
  "issns": [
    "1553-7374"
  ],
  "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014587",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2804|Neuropeptides and Animal Physiology"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Digestive system/Gastrointestinal tract"
    ],
    [
      "plos",
      "/Biology and life sciences/Anatomy/Digestive system/Gastrointestinal tract/Colon"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Hormones/Peptide hormones/Neuropeptides"
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      "plos",
      "/Biology and life sciences/Biochemistry/Neurochemistry/Neurochemicals/Neuropeptides"
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      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/T cells"
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      "plos",
      "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/T cells"
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      "/Biology and life sciences/Immunology/Immune response/Inflammation"
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      "/Biology and life sciences/Immunology/Immune system/Innate immune system/Cytokines"
    ],
    [
      "plos",
      "/Biology and life sciences/Neuroscience/Neurochemistry/Neurochemicals/Neuropeptides"
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    ],
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      "plos",
      "/Medicine and health sciences/Anatomy/Digestive system/Gastrointestinal tract/Colon"
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      "plos",
      "/Medicine and health sciences/Clinical medicine/Signs and symptoms/Inflammation"
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      "/Medicine and health sciences/Immunology/Immune cells/White blood cells/T cells"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune response"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune response/Inflammation"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune system/Innate immune system/Cytokines"
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  "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014587&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-18",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/7bz2v5czjma59.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1371/journal.ppat.1014587",
      "source": "plos",
      "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014587"
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  "subjects": [
    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
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    {
      "field": "medicine",
      "origin": "plos:anatomy",
      "subfield": "physiology"
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  "title": "Tac1 deficiency reduces the severity of enteric bacterial infection",
  "title_text": "Tac1 deficiency reduces the severity of enteric bacterial infection",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/7bz2v5czjma59",
  "venue": "PLOS Pathogens",
  "versions": []
}