{
  "abstract": "Serious pertussis infections disproportionately affect infants but the biological basis for this age-dependent susceptibility remains unclear. Infant mouse models recapitulate features of severe human infant pertussis. We investigated the role of interferon lambda (IFN-{lambda}), a key regulator of mucosal immunity, in Bordetella pertussis infection of infant mice. While infected adult mice upregulate lung IFN-{lambda}, infant mice inoculated at P7 fail to upregulate IFN-{lambda} and succumb to infection. We hypothesized that failure to produce IFN-{lambda} during infection represents a critical immunological deficit in infant mice, and that restoring IFN-{lambda} signaling would improve survival outcomes. Whereas wild-type mice gained complete protection from lethal B. pertussis infection by P10, mice lacking the IFN-{lambda} receptor component IFNLR1 did not achieve full protection until P21. Loss of IFNLR1 was associated with enhanced bacterial dissemination to systemic organs. Infant mice possessed a functional IFN-{lambda} receptor in the lungs but failed to upregulate IFN-{lambda} during infection, and supplementing IFN-{lambda} exogenously extended survival. RNA sequencing of lung tissue from infected and uninfected wild-type and IFNLR1-deficient mice inoculated at different ages identified an immune transcriptional framework distinguishing susceptible from resistant animals at a systems level and revealed IFN-{lambda} signaling as a critical driver of immunological maturation in the infant lung. Infected infant IFNLR1-deficient mice had dysregulated immune cell recruitment to the lungs, indicating a quantitatively expanded but qualitatively impaired response. These findings demonstrate that IFN-{lambda} affects immune maturation accounting for a critical window of age-dependent resistance to lethal pertussis with novel therapeutic possibilities for human infants with this disease.",
  "abstract_shown": true,
  "affiliations": [
    "University of Maryland School of Medicine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "name": "D. Johnson"
    },
    {
      "affs": [
        0
      ],
      "name": "N. H. Carbonetti"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fh7r31jzkmxez.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.22.753444",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753444v1.full",
  "id": "fh7r31jzkmxez",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753444v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2403|interferon and immune responses"
    ]
  ],
  "openalex": "W7214602798",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753444v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fh7r31jzkmxez.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:53Z",
      "native_id": "10.64898/2026.09.22.753444",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753444v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Interferon lambda drives immunological maturation in the infant lung and protects against lethal Bordetella pertussis infection",
  "title_text": "Interferon lambda drives immunological maturation in the infant lung and protects against lethal Bordetella pertussis infection",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:53Z",
  "url": "https://research.draconitic.com/paper/fh7r31jzkmxez",
  "venue": "bioRxiv",
  "versions": []
}