{
  "abstract": "Background: Once viewed mainly as scavengers of innate immunity, macrophages are now recognized as constitutive partners of the nervous system. In neural tissue their identity is instructed by neurons and glia, and in turn they shape neural function — pruning synapses, tuning neuronal excitability, and executing the autonomic commands that restrain inflammation.\n\nPurpose: Here we advance a mechanistic model built on three principles: that neural and glial signals specify macrophage identity on a shared myeloid template; that the macrophage is a bidirectional sensor–effector node within autonomic reflex arcs, both relaying neural output and generating the cytokine signals that afferent nerves detect; and that this sensor–effector arc is modular, recurring across brain, spleen, gut, heart, and adipose tissue. We give particular attention to the afferent limb of the inflammatory reflex, which now extends beyond the vagus to nociceptors and to the carotid body, an arterial chemoreceptor that senses circulating inflammatory signals and recruits a sympathetic anti-inflammatory pathway, and to the stress-responsive circuitry through which sympathetic outflow drives myelopoiesis, neuroinflammation, and sickness behavior. We then turn to disease, in which macrophage function is altered by a diseased or aged niche in neurodegeneration, chronic pain, gut–brain disorders, and metabolic disease.\n\nConclusions: Whether the neuroimmune circuits described here are themselves disrupted in these conditions, rather than merely coexisting with them, is largely untested, and we outline what such evidence would require. We close by arguing that tuning these circuits, rather than broadly suppressing macrophage activity, is the more plausible therapeutic goal.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Physiology and Pathology, School of Dentistry, São Paulo State University (UNESP), Rua Humaitá 1680, Araraquara, 14801-903 São Paulo Brazil"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Renato S. da Cruz"
    },
    {
      "affs": [
        0
      ],
      "name": "Luana S. Lopes"
    },
    {
      "affs": [
        0
      ],
      "name": "Alec N. S. Pachiega"
    },
    {
      "affs": [
        0
      ],
      "name": "Débora S. A. Colombari"
    },
    {
      "affs": [
        0
      ],
      "name": "Eduardo Colombari"
    },
    {
      "affs": [
        0
      ],
      "name": "Daniel B. Zoccal"
    },
    {
      "affs": [
        0
      ],
      "name": "Pedro L. Katayama"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3rc2xd4eedd9b.bib",
  "cited_by": 0,
  "doi": "10.1007/s00011-026-02401-8",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696598/",
  "id": "3rc2xd4eedd9b",
  "issns": [
    "1023-3830",
    "1420-908X"
  ],
  "landing_url": "https://doi.org/10.1007/s00011-026-02401-8",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review"
    ],
    [
      "openalex",
      "2808|Vagus Nerve Stimulation Research"
    ]
  ],
  "openalex": "W7223562029",
  "pdf_url": "https://europepmc.org/articles/PMC13696598?pdf=render",
  "pmcid": "PMC13696598",
  "pmid": "42928276",
  "published": "2026-10-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3rc2xd4eedd9b.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:55Z",
      "native_id": "PMC13696598",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s00011-026-02401-8"
    },
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42928276",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42928276"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2808|Vagus Nerve Stimulation Research",
      "subfield": "neurology"
    }
  ],
  "title": "The macrophage as a neuroimmune sensor and effector: neural control of inflammation across tissues and disease",
  "title_text": "The macrophage as a neuroimmune sensor and effector: neural control of inflammation across tissues and disease",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:33:54Z",
  "url": "https://research.draconitic.com/paper/3rc2xd4eedd9b",
  "venue": "Inflammation Research",
  "versions": []
}