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Blood, 15 September 2004, Vol. 104, No. 6, pp. 1778-1783. Prepublished online as a Blood First Edition Paper on May 27, 2004; DOI 10.1182/blood-2003-08-2820. This Article Full Text (PDF) All Versions of this Article: 2003-08-2820v1 104/6/1778    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 Chalifour, A. Articles by Delneste, Y. Search for Related Content PubMed PubMed Citation Articles by Chalifour, A. Articles by Delneste, Y. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 15, 2003 Accepted April 13, 2004 Direct bacterial protein PAMPs recognition by human NK cells involves TLRs and triggers -defensin production Anick Chalifour, Pascale Jeannin, Jean-Francois Gauchat, Aline Blaecke, Martine Malissard, Thien N'Guyen, Nathalie Thieblemont, and Yves Delneste* Cancerologie Experimentale, Centre Immunologie Pierre Fabre, St-Julien-en-Genevois, France Cancerologie Experimentale, Centre Immunologie Pierre Fabre, St-Julien-en-Genevois, France; INSERM U564, Angers, France CNRS-FRE 2444, Paris, France * Corresponding author; email: yves.delneste{at}med.univ-angers.fr. Although human CD56+CD3- NK cells participate to immune responses against microorganisms, their capacity to directly recognize and be activated by pathogens remains unclear. These cells encode members of the Toll-like receptor (TLR) family, involved in innate cell activation upon recognition of pathogen-associated molecular patterns (PAMPs). We therefore evaluated whether the two bacterial protein PAMPs, the outer membrane protein A from Klebsiella pneumoniae (KpOmpA) and flagellin, which signal via TLR2 and TLR5, respectively, may directly stimulate human NK cells. These proteins induce IFN production by NK cells and synergize with IL-2 and pro-inflammatory cytokines in PAMPs-induced activation. Similar results were obtained using CD56+CD3+ (NKR-expressing) T cells. NK cells from TLR2-/- mice fail to respond to KpOmpA, demonstrating TLR involvement in this effect. Defensins are antimicrobial peptides expressed mainly by epithelial cells and neutrophils that disrupt bacterial membrane, leading to pathogen death. We show that NK cells and NKR-expressing T cells constitutively express -defensins and that KpOmpA and flagellin rapidly induce their release. These data demonstrate for the first time that highly purified NK cells directly recognize and respond to pathogen components via TLRs and also evidence defensins as a novel and direct cytotoxic pathway involved in NK cell-mediated protection against microorganisms. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. N. Toka, C. K. Nfon, H. Dawson, and W. T. Golde Accessory-Cell-Mediated Activation of Porcine NK Cells by Toll-Like Receptor 7 (TLR7) and TLR8 Agonists Clin. Vaccine Immunol., June 1, 2009; 16(6): 866 - 878. [Abstract] [Full Text] [PDF] C. L. Wilson, A. P. Schmidt, E. Pirila, E. V. Valore, N. Ferri, T. Sorsa, T. Ganz, and W. C. Parks Differential Processing of {alpha}- and {beta}-Defensin Precursors by Matrix Metalloproteinase-7 (MMP-7) J. Biol. Chem., March 27, 2009; 284(13): 8301 - 8311. [Abstract] [Full Text] [PDF] P. M. Drake, J. K. Nathan, C. M. Stock, P. V. Chang, M. O. Muench, D. 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