{
  "abstract": "Coxiella burnetii ( Cb ), the causative agent of Q fever, replicates within host macrophages by modulating innate immune responses through its type IVB secretion system (T4SS). Host cells sense pathogens via Pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), to recognize pathogen-associated molecular patterns (PAMPs) and initiate signaling pathways that drive pro-inflammatory cytokine and interferon responses. Toll-like receptor 3 (TLR3) triggers the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-{kappa}B) and Interferon regulatory factors (IRFs) resulting in pro-inflammatory cytokine production and type I interferon (IFN-I) induction. Here we demonstrate that Cb requires T4SS to suppress TLR3-induced NF-{kappa}B and IRF transcriptional responses. Furthermore, RNA purified from both virulent and avirulent Cb is sufficient to activate TLR3, identifying pathogen RNA as a relevant PAMP in this context. Using a pulmonary infection model with virulent Cb, we found that TLR3/ Toll-Interleukin-1 Receptor Domain-Containing Adapter Protein Inducing Interferon Beta (TRIF)-dependent innate immune pathway inhibits cachexia. In contrast, signaling through the interferon-/{beta} receptor (IFNAR) restricts bacterial dissemination, indicating that these pathways play distinct but complementary roles in host defense. Mechanistically, Cb suppresses TLR3/TRIF signaling in a T4SS-dependent manner by preventing host TLR3 recruitment to the Coxiella-containing vacuole (CCV) and disrupting TRIF-TNF Receptor-Associated Factor 6 (TRAF6) interactions, thereby selectively inhibiting impairing NF-{kappa}B activation. Consistent with this, we identify five T4SS effector proteins that attenuate TLR3-induced NF-{kappa}B signaling, including CBU1292, which suppresses both NF-{kappa}B and IRF-dependent responses downstream of TLR3.",
  "abstract_shown": true,
  "affiliations": [
    "Texas A&M University System Health Science Center College of Medicine: Texas A&M University School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "J. E. Samuel"
    },
    {
      "name": "S. Mahapatra"
    },
    {
      "name": "A. Arunima"
    },
    {
      "name": "A. Busbee"
    },
    {
      "name": "J. Dumaine"
    },
    {
      "name": "L. Stranahan"
    },
    {
      "name": "R. Zeledon"
    },
    {
      "name": "B. Dow"
    },
    {
      "name": "S. Butler"
    },
    {
      "name": "S. Clark"
    },
    {
      "name": "P. West"
    },
    {
      "name": "E. van Schaik"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/anmmbsf4xt3hn.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.23.753975",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753975v1.full",
  "id": "anmmbsf4xt3hn",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753975v1",
  "language": null,
  "licence": "CC0-1.0",
  "licence_label": "CC0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/publicdomain/zero/1.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "2403|Immune Response and Inflammation"
    ]
  ],
  "openalex": "W7214206793",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753975v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/anmmbsf4xt3hn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:25Z",
      "native_id": "10.64898/2026.09.23.753975",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753975v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Coxiella burnetii type IVB secretion system modulates TLR3/TRIF-dependent NF-κB and IRF responses during infection",
  "title_text": "Coxiella burnetii type IVB secretion system modulates TLR3/TRIF-dependent NF-κB and IRF responses during infection",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:25Z",
  "url": "https://research.draconitic.com/paper/anmmbsf4xt3hn",
  "venue": "bioRxiv",
  "versions": []
}