{
  "abstract": "Severe dengue is characterized by systemic inflammation and vascular leakage. Recent evidence indicates that Toll-like receptor 2 (TLR2) supports early steps of dengue virus (DENV) infection in monocytes, whereas intracellular viral RNA sensing drives much of the subsequent inflammatory response. However, whether this entry-associated function of TLR2 differs among human monocyte subsets remains unknown. Here, we investigated how the TLR2 axis regulates DENV serotype 2 (DENV2) infection and inflammatory output in purified primary human monocytes and sorted monocyte subsets. Blocking TLR2 at the cell surface or targeting its intracellular TIR domain reduced virus-cell association, productive infection, and the release of inflammatory and antiviral mediators. Among TLR2-associated receptors, CD14 and, to a lesser extent, CD36 contributed to efficient infection, whereas TLR1, TLR6, and TLR10 were dispensable under the conditions tested. Notably, TLR2 blockade reduced viral production and cytokine release in CD16- classical monocytes but not in pooled CD16+ monocytes, identifying a subset-specific dependence on the TLR2 axis. TLR3 contributed to inflammatory and antiviral responses without affecting viral replication, consistent with post-entry recognition of viral RNA. Finally, blocking the TLR2 axis during monocyte infection prevented the loss of endothelial barrier integrity induced by monocyte-derived soluble mediators. Together, these findings identify a TLR2-associated entry route that preferentially supports productive DENV2 infection in classical monocytes and thereby enables RNA-sensor-dependent inflammatory responses that compromise endothelial function.",
  "abstract_shown": true,
  "affiliations": [
    "University Medical Center Groningen"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "J. A. Castillo"
    },
    {
      "name": "M. Punekar"
    },
    {
      "name": "V. Upasani"
    },
    {
      "name": "P. van Duinkerken"
    },
    {
      "name": "B. ter Ellen"
    },
    {
      "name": "H. van der Ende-Metselaar"
    },
    {
      "name": "S. Urcuqui-Inchima"
    },
    {
      "name": "J. M. Smit"
    },
    {
      "affs": [
        0
      ],
      "name": "I. A. Rodenhuis-Zybert"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a0zcp7nmnkq8c.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.30.755835",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755835v1.full",
  "id": "a0zcp7nmnkq8c",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755835v1",
  "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",
      "microbiology"
    ],
    [
      "openalex",
      "2403|Immune Response and Inflammation"
    ]
  ],
  "openalex": "W7219074404",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755835v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/a0zcp7nmnkq8c.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:53Z",
      "native_id": "10.64898/2026.09.30.755835",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.30.755835v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "A TLR2-associated entry pathway promotes productive dengue virus serotype 2 infection and inflammatory responses in classical monocytes",
  "title_text": "A TLR2-associated entry pathway promotes productive dengue virus serotype 2 infection and inflammatory responses in classical monocytes",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:53Z",
  "url": "https://research.draconitic.com/paper/a0zcp7nmnkq8c",
  "venue": "bioRxiv",
  "versions": []
}