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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1284-1290. Prepublished online as a Blood First Edition Paper on April 25, 2006; DOI 10.1182/blood-2005-12-4821. This Article Full Text (PDF) Supplemental Tables All Versions of this Article: 2005-12-4821v1 108/4/1284    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 Levy, O. Articles by Wessels, M. R Search for Related Content PubMed PubMed Citation Articles by Levy, O. Articles by Wessels, M. R Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 6, 2005 Accepted March 28, 2006 Unique efficacy of Toll-like receptor 8 agonists in activating human neonatal antigen-presenting cells Ofer Levy*, Eugenie E Suter, Richard L Miller, and Michael R Wessels Division of Infectious Diseases, Children's Hospital Boston, Boston, MA, USA; Harvard Medical School, Boston, MA, USA Division of Infectious Diseases, Children's Hospital Boston, Boston, MA, USA 3M Pharmaceuticals, St. Paul, MN, USA * Corresponding author; email: ofer.levy{at}childrens.harvard.edu. Newborns are prone to microbial infection and have poor memory responses to multiple antigens. We have previously shown that human neonatal blood monocytes exhibit impaired TNF- responses to most known TLR agonists, including the pure TLR7 agonist imiquimod (Levy et al J. Immunol. 173: 4627-34). Surprisingly, however, neonatal TNF- responses to the imiquimod congener R-848 (TLR 7/8) were fully intact. We now show that TLR8 agonists, including R-848 (TLR7/8), the imidazoquinoline congeners 3M-003 (TLR7/8) and 3M-002 (TLR8), as well as single stranded viral RNAs (TLR8) induced robust production of the Th1-polarizing cytokines TNF- and IL-12 from neonatal APCs that substantially exceeds responses induced by TLR-2, -4, or -7 (alone) agonists. TLR8 agonists also effectively induced up-regulation of the co-stimulatory molecule CD40 on neonatal and adult myeloid DCs. The strong activity of TLR8 agonists correlates with their induction of p38 MAP kinase phosphorylation and with degradation of IB- in both neonatal and adult monocytes. We conclude that TLR8 agonists are uniquely efficacious in activating co-stimulatory responses in neonatal APCs and suggest that these agents are promising candidate adjuvants for enhancing immune responses in human newborns. 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