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Blood, 1 September 2008, Vol. 112, No. 5, pp. 1750-1758. Prepublished online as a Blood First Edition Paper on June 30, 2008; DOI 10.1182/blood-2008-01-130500. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2008-01-130500v1 112/5/1750    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wynn, J. L. Articles by Moldawer, L. L. Search for Related Content PubMed PubMed Citation Articles by Wynn, J. L. Articles by Moldawer, L. L. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Defective innate immunity predisposes murine neonates to poor sepsis outcome but is reversed by TLR agonists James L. Wynn1,2, Philip O. Scumpia1, Robert D. Winfield1, Matthew J. Delano1, Kindra Kelly-Scumpia1, Tolga Barker3, Ricardo Ungaro1, Ofer Levy4, and Lyle L. Moldawer1 From the Departments of1 Surgery, 2 Pediatrics, and 3 Medicine, University of Florida College of Medicine, Gainesville; and 4 Department of Medicine, Division of Infectious Disease, Children's Hospital Boston and Harvard Medical School, Boston, MA Neonates exhibit an increased risk of sepsis mortality compared with adults. We show that in contrast to adults, survival from polymicrobial sepsis in murine neonates does not depend on an intact adaptive immune system and is not improved by T cell–directed adaptive immunotherapy. Furthermore, neonates manifest an attenuated inflammatory and innate response to sepsis, and have functional defects in their peritoneal CD11b+ cells. Activation of innate immunity with either a Toll-like receptor 4 (TLR4) or TLR7/8 agonist, but not a TLR3 agonist, increased the magnitude, but abbreviated the early systemic inflammatory response, reduced bacteremia, and improved survival to polymicrobial sepsis. TLR4 agonist pretreatment enhanced peritoneal neutrophil recruitment with increased oxidative burst production, whereas the TLR7/8 agonist also enhanced peritoneal neutrophil recruitment with increased phagocytic ability. These benefits were independent of the adaptive immune system and type I interferon signaling. Improving innate immune function with select TLR agonists may be a useful strategy to prevent neonatal sepsis mortality. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. C. Yost, M. J. Cody, E. S. Harris, N. L. Thornton, A. M. McInturff, M. L. Martinez, N. B. Chandler, C. K. Rodesch, K. H. Albertine, C. A. Petti, et al. Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates Blood, June 18, 2009; 113(25): 6419 - 6427. [Abstract] [Full Text] [PDF]

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