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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2360-2368. Prepublished online as a Blood First Edition Paper on June 26, 2008; DOI 10.1182/blood-2008-02-137711. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-02-137711v1 112/6/2360    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 Ahmad, R. Articles by Menezes, J. Search for Related Content PubMed PubMed Citation Articles by Ahmad, R. Articles by Menezes, J. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Requirement of TLR2-mediated signaling for the induction of IL-15 gene expression in human monocytic cells by HSV-1 Rasheed Ahmad1,*, Souad El Bassam1,*, Paulo Cordeiro1, and José Menezes1 1 Laboratory of Immunovirology and Viral & Immune Diseases Program, Ste-Justine Hospital Research Center and Department of Microbiology & Immunology, Faculty of Medicine, University of Montreal, Montreal, QC Exposure of human monocytic cells to herpes simplex virus type 1 (HSV-1) results in immediate up-regulation of interleukin (IL)–15 gene expression. However, the receptor involved in this induction is not known. Here, we provide evidence that this induction depends on TLR2-mediated signaling pathway. Through the use of small interfering RNAs (siRNAs), we demonstrate that HSV-1–induced up-regulation of IL-15 gene expression in monocytic THP1 cells requires the presence of the adaptors MyD88, IRAK1, and TRAF6. Interestingly, TIRAP/Mal, an adaptor molecule specifically recruited to TLR2 and TLR4, was also required for maximal up-regulation of IL-15. This response was completely abrogated by anti-TLR2, but not anti-TLR4, blocking mAbs in both primary monocytes and THP1 cells. Furthermore, THP1 cells rendered defective in TLR2 expression by disrupting the expression of Sp1, a major transcription factor involved in TLR2 promoter activity, were unable to up-regulate IL-15 gene expression in response to HSV-1. In addition, HSV-1–induced NF-B activation was significantly reduced after neutralization of TLR2 and the adaptor proteins. Altogether, these results unequivocally show that HSV-1 induces TLR2-dependent activation of IL-15 gene expression, which requires the recruitment of both MyD88 and TIRAP/Mal and the activation of IRAK1 and TRAF6 leading to NF-B translocation to the nucleus. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. G. Frey, C. M. I. Ahmed, R. Dabelic, L. D. Jager, E. N. Noon-Song, S. M. Haider, H. M. Johnson, and N. J. Bigley HSV-1-Induced SOCS-1 Expression in Keratinocytes: Use of a SOCS-1 Antagonist to Block a Novel Mechanism of Viral Immune Evasion J. Immunol., July 15, 2009; 183(2): 1253 - 1262. [Abstract] [Full Text] [PDF] J. Giron-Michel, F. Menard, S. Negrini, A. Devocelle, B. Azzarone, and C. Besson EBV-associated mononucleosis does not induce long-term global deficit in T-cell responsiveness to IL-15 Blood, May 7, 2009; 113(19): 4541 - 4547. [Abstract] [Full Text] [PDF] D. Piccioli, C. Sammicheli, S. Tavarini, S. Nuti, E. Frigimelica, A. G.O. Manetti, A. Nuccitelli, S. Aprea, S. Valentini, E. Borgogni, et al. Human plasmacytoid dendritic cells are unresponsive to bacterial stimulation and require a novel type of cooperation with myeloid dendritic cells for maturation Blood, April 30, 2009; 113(18): 4232 - 4239. [Abstract] [Full Text] [PDF]

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