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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 4, 2008 Accepted June 20, 2008 Defective innate immunity predisposes murine neonates to poor sepsis outcome, but is reversed by TLR agonists James L Wynn, Philip O Scumpia, Robert D Winfield, Matthew J Delano, Kindra Kelly-Scumpia, Tolga Barker, Ricardo Ungaro, Ofer Levy, and Lyle L Moldawer* Department of Pediatrics, University of Florida, Gainesville, Florida, United States Department of Surgery, University of Florida, Gainesville, Florida, United States Department of Medicine, University of Florida, Gainesville, Florida, United States Department of Medicine, Division of Infectious Disease, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, United States * Corresponding author; email: moldawer{at}surgery.ufl.edu. Neonates exhibit an increased risk of sepsis mortality compared to 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 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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