{
  "abstract": "The cell-intrinsic complement system has emerged as an important orchestrator of a variety of cell-physiological processes, with complement components interacting with intracellular effector systems to regulate cellular responses to pathogens or noxious stimuli. For instance, intracellular C5 signaling through a mitochondrial C5a receptor (C5aR1) controls IL-1{beta} production in human monocytes and macrophages. Here, we investigated whether cell-intrinsic C3 similarly regulates inflammatory responses in macrophages. In LPS-stimulated C3 knockout THP-1-derived macrophages, interferon (IFN)-{beta} production was increased, accompanied by elevated expression of interferon-stimulated genes and enhanced secretion of IFN-induced cytokines and chemokines. C3-deficient cells showed increased phosphorylation of IRF3 at Ser396 and a stabilization of the interaction between IRF3 and TBK1, along with enhanced IRF3 dimerization and nuclear translocation. TBK1 phosphorylation was unaffected, indicating that C3 limits IRF3-TBK1 complex formation rather than upstream TBK1 activation. Small-molecule inhibitors of complement factors B and D restored full-length C3 abundance in LPS-stimulated primary human macrophages, consistent with inhibition of the C3 convertase. It also reduced LPS-induced IFN-{beta} production in primary human macrophages and THP-1 cells, suggesting that full-length, uncleaved C3 suppresses IFN-{beta} production. Collectively, these findings identify cell-intrinsic C3 as a suppressor of IFN-{beta} production in human macrophages, highlighting the importance of the cell-intrinsic complement system in fine-tuning inflammatory responses to pathogens.",
  "abstract_shown": true,
  "affiliations": [
    "Norwegian University of Science and Technology"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "S. Kristensen"
    },
    {
      "name": "C. Arseth"
    },
    {
      "name": "M. Yurchenko"
    },
    {
      "name": "L. Ryan"
    },
    {
      "name": "I. Fjellvaer"
    },
    {
      "name": "K. Rasheed"
    },
    {
      "name": "S. Ullmann"
    },
    {
      "name": "C. Kemper"
    },
    {
      "name": "H. Husebye"
    },
    {
      "name": "T. Espevik"
    },
    {
      "affs": [
        0
      ],
      "name": "T. H. Flo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/88y37yqhw9426.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.26.746684",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.26.746684v1.full",
  "id": "88y37yqhw9426",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.26.746684v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2403|interferon and immune responses"
    ]
  ],
  "openalex": "W7204801613",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.26.746684v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-26",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/88y37yqhw9426.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:19Z",
      "native_id": "10.64898/2026.08.26.746684",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.26.746684v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Cell-intrinsic complement C3 suppresses IFN-β production in macrophages",
  "title_text": "Cell-intrinsic complement C3 suppresses IFN-β production in macrophages",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:19Z",
  "url": "https://research.draconitic.com/paper/88y37yqhw9426",
  "venue": "bioRxiv",
  "versions": []
}