{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:57:29Z","timestamp":1790866649322,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,28]]},"group-title":"Immunology","reference-count":80,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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-\u03bb), a key regulator of mucosal immunity, in\n                  <jats:italic>Bordetella pertussis<\/jats:italic>\n                  infection of infant mice. While infected adult mice upregulate lung IFN-\u03bb, infant mice inoculated at P7 fail to upregulate IFN-\u03bb and succumb to infection. We hypothesized that failure to produce IFN-\u03bb during infection represents a critical immunological deficit in infant mice, and that restoring IFN-\u03bb signaling would improve survival outcomes. Whereas wild-type mice gained complete protection from lethal\n                  <jats:italic>B. pertussis<\/jats:italic>\n                  infection by P10, mice lacking the IFN-\u03bb 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-\u03bb receptor in the lungs but failed to upregulate IFN-\u03bb during infection, and supplementing IFN-\u03bb 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-\u03bb 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-\u03bb 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.\n                <\/jats:p>","DOI":"10.64898\/2026.09.22.753444","type":"posted-content","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:35:17Z","timestamp":1790609717000},"source":"Crossref","is-referenced-by-count":0,"title":["Interferon lambda drives immunological maturation in the infant lung and protects against lethal\n                  <i>Bordetella pertussis<\/i>\n                  infection"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7738-5507","authenticated-orcid":false,"given":"Da\u2019Kuawn","family":"Johnson","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, 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