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Blood, 1 April 2007, Vol. 109, No. 7, pp. 2675-2676. This Article Full Text (PDF) 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 Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bortolussi, R. Search for Related Content PubMed Articles by Bortolussi, R. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  INSIDE BLOOD Comment on Aksoy et al, page 2887 Brave new world: birth of immunity Robert Bortolussi DALHOUSIE UNIVERSITY In this issue of Blood, Aksoy and colleagues contribute to the understanding of remarkable immunoregulatory controls at the time of birth by showing that impaired synthesis of interferon-ß (IFNß) and IFN-inducible factors elicited by lipopolysaccharide (LPS) depends on the transcriptional activity of interferon regulatory factor 3 (IRF-3) downstream of Toll-like receptor-4 (TLR4). The human newborn is profoundly susceptible to intracellular bacterial pathogens that require Th1-dependent host defense pathways for eradication. The molecular basis for the newborn's attenuated response to such infections remains a mystery but is likely a consequence of the immunosuppression required for survival in utero. In this article, Aksoy and colleagues show that an impaired response of monocyte-derived dendritic cells (moDCs) from newborns to LPS (at concentrations that occur during bacterial sepsis) depends on transcriptional activity downstream of Toll-like receptor 4 (TLR4) that is independent of myeloid differentiation factor 88 (MyD88). In addition, LPS fails to induce synthesis of IFNß in cord blood at levels that are clearly detected in adult blood. In line with this seminal observation, the induction of CXCL10—a prototypic IFN-dependent gene—was diminished in cord blood. In contrast, induction of IL-1ß and IL-6 mRNA by LPS is comparable in cord and adult blood. Specificity of this deficiency was shown by demonstrating that genes that depend on MyD88 (NF-B activation) were similar after LPS stimulation for adult and newborn moDCs. The authors also demonstrate that LPS-induced translocation of interferon regulatory factor 3 (IRF-3) to the nucleus occurred in both adult and neonatal moDCs. However, IRF-3 DNA binding to the coactivator CREB-binding protein (CBP) was decreased in neonatal compared with adult moDCs. The authors concluded that deficient IRF-3/CBP interaction in LPS-stimulated neonatal moDCs may reduce their ability to elicit Th1 responses. The findings are relevant to our understanding of immunosuppression in utero and in early life but have not been tested in an in vivo experimental model. The timing and the processes involved in the transition to mature form of immunity remain areas for further discovery. Footnotes The author declares no competing financial interests. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Interferon regulatory factor 3-dependent responses to lipopolysaccharide are selectively blunted in cord blood cells Ezra Aksoy, Valentina Albarani, Muriel Nguyen, Jean-Francois Laes, Jean-Louis Ruelle, Dominique De Wit, Fabienne Willems, Michel Goldman, and Stanislas Goriely Blood 2007 109: 2887-2893. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) 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 Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bortolussi, R. Search for Related Content PubMed Articles by Bortolussi, R. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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