{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:00:49Z","timestamp":1787162449389,"version":"build-2736575974"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,2,1]],"date-time":"2015-02-01T00:00:00Z","timestamp":1422748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Current evidence suggests that neonatal immunity is functionally distinct from adults. Although TLR signaling through the adaptor protein, MyD88, has been shown to be critical for survival to sepsis in adults, little is known about the role of MyD88 or TRIF in neonatal sepsis. We demonstrate that TRIF\u2212\/\u2212 but not MyD88\u2212\/\u2212 neonates are highly susceptible to Escherichia coli peritonitis and bacteremia. This was associated with decreased innate immune recruitment and function. Importantly, we found that the reverse was true in adults that MyD88\u2212\/\u2212 but not TRIF\u2212\/\u2212 or wild-type adults are susceptible to E. coli peritonitis and bacteremia. In addition, we demonstrate that TRIF but not MyD88 signaling is critical for the TLR4 protective adjuvant effect we have previously demonstrated. These data suggest a differential requirement for the survival of neonates versus adults to Gram-negative infection, and that modulation of TRIF in neonates can be used to augment survival to neonatal sepsis.<\/jats:p>","DOI":"10.4049\/jimmunol.1302676","type":"journal-article","created":{"date-parts":[[2014,12,30]],"date-time":"2014-12-30T03:27:26Z","timestamp":1419910046000},"page":"1169-1177","source":"Crossref","is-referenced-by-count":25,"title":["TRIF-Dependent Innate Immune Activation Is Critical for Survival to Neonatal Gram-Negative Sepsis"],"prefix":"10.1093","volume":"194","author":[{"given":"Alex G","family":"Cuenca","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine and Dentistry , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dallas N","family":"Joiner","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine and Dentistry , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori F","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine and Dentistry , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela L","family":"Cuenca","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine and Dentistry , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L","family":"Wynn","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics Vanderbilt University , Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kindra M","family":"Kelly-Scumpia","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine and Dentistry , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip O","family":"Scumpia","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine and Dentistry , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin E","family":"Behrns","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine and Dentistry , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip A","family":"Efron","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine and Dentistry , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Nacionales","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine and Dentistry , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Lui","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Florida College of Medicine and Dentistry , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon M","family":"Wallet","sequence":"additional","affiliation":[{"name":"University of Florida College of Medicine and Dentistry , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Westley H","family":"Reeves","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Florida College of Medicine and Dentistry , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton E","family":"Mathews","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Florida College of Medicine and Dentistry , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyle L","family":"Moldawer","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine and Dentistry , Gainesville, FL 32610"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,2,1]]},"reference":[{"key":"2025030704582213600_r1","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1093\/ije\/dyl043","article-title":"Estimating the causes of 4 million neonatal deaths in the year 2000","volume":"35","author":"Lawn","year":"2006","journal-title":"Int. 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