{
  "abstract": "The NLRP3 inflammasome contributes to a wide range of conditions from infections to Alzheimer's disease. NLRP3 forms an inactive decameric cage, that upon interaction with the trans-Golgi network (TGN) and microtubule organization center (MTOC), leads to inflammasome activation, yet whether non-decamer NLRP3 species form functional inflammasomes remains unclear. Here, we design a NLRP3 exon 3 deletion variant that forms low molecular weight NLRP3 assemblies. Spatially and dynamically highly resolved microscopy in THP-1 and human macrophages shows that nigericin, a K +dependent NLRP3 stimulus, can trigger two distinct activation pathways: (i) the rapidly engaged decameric cage-dependent pathway; and (ii) a decameric cage-independent, TGN/MTOC-distal, and slow-reacting pathway employed by low molecular weight NLRP3 species, that dominates in human neutrophils. Collectively, our results delineate two parallel yet biologically distinct NLRP3 activation pathways, thereby providing a framework to understand NLRP3-driven inflammation across a wide range of pathological context and cell types.Inflammation is an essential innate immune response that enables rapid defense against infection and tissue damage. Central to this process are inflammatory cytokines of the interleukin-1 (IL-1) family, whose maturation and release are controlled by cytosolic multiprotein complexes named inflammasomes, assembled in immune cells such as macrophages or neutrophils 1 . Among them, the nucleotide-binding domain and leucine-rich repeat pyrin domain-containing protein 3 (NLRP3) inflammasome is the most extensively studied and is strongly associated with human disease. NLRP3 gain-of-function mutations cause autoinflammatory disorders collectively termed Cryopyrin-Associated Periodic Syndromes (CAPS) 2,3 . Furthermore, aberrant activation of NLRP3 contributes to a broad spectrum of conditions ranging from gout to Alzheimer's disease 4 . The clinical relevance of this pathway has driven extensive efforts to elucidate the molecular mechanism",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "María Mateo-Tórtola"
    },
    {
      "name": "Inga V Hochheiser"
    },
    {
      "name": "Gaopeng Li"
    },
    {
      "name": "Lukas Funk"
    },
    {
      "name": "Atousa Hashemi"
    },
    {
      "name": "Xiao Liu"
    },
    {
      "name": "Jane Torp"
    },
    {
      "name": "Lena Erlebach"
    },
    {
      "name": "András Szolek"
    },
    {
      "name": "Jelena Grga"
    },
    {
      "name": "Francesca Bork"
    },
    {
      "name": "Jana S Müller"
    },
    {
      "name": "Deborah Kronenberg-Versteeg"
    },
    {
      "name": "Matthias Geyer"
    },
    {
      "name": "Alexander N R Weber"
    },
    {
      "name": "Ana Tapia-Abellán"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2zcyngk7tcbkg.bib",
  "cited_by": 3,
  "doi": "10.1038/s41467-026-72627-x",
  "fulltext_url": null,
  "id": "2zcyngk7tcbkg",
  "issns": [
    "2041-1723",
    "2041-1723"
  ],
  "landing_url": "https://hal.inrae.fr/hal-05781591v1",
  "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": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.bbm"
    ],
    [
      "hal",
      "1.sdv.bc"
    ],
    [
      "hal",
      "1.sdv.mhep"
    ],
    [
      "hal",
      "2.sdv.bc.bc"
    ],
    [
      "openalex",
      "1312|Inflammasome and immune disorders"
    ]
  ],
  "openalex": "W7162767473",
  "pdf_url": "https://hal.inrae.fr/hal-05781591/document",
  "pmcid": null,
  "pmid": "42215451",
  "published": "2026-05-30",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/2zcyngk7tcbkg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "hal-05781591",
      "source": "hal",
      "url": "https://hal.inrae.fr/hal-05781591v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "hal:1.sdv.bbm",
      "subfield": "general"
    },
    {
      "field": "biology",
      "origin": "hal:1.sdv.bc",
      "subfield": "cell-biology"
    },
    {
      "field": "medicine",
      "origin": "hal:1.sdv.mhep",
      "subfield": "general"
    }
  ],
  "title": "Non-decameric NLRP3 reveals a TGN/MTOC-distal pathway of inflammasome activation",
  "title_text": "Non-decameric NLRP3 reveals a TGN/MTOC-distal pathway of inflammasome activation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/2zcyngk7tcbkg",
  "venue": "Nature Communications",
  "versions": []
}