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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 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 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 Chalifour, A. Articles by Delneste, Y. Search for Related Content PubMed PubMed Citation Articles by Chalifour, A. Articles by Delneste, Y. Related Collections Immunobiology Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Direct bacterial protein PAMP recognition by human NK cells involves TLRs and triggers -defensin production Anick Chalifour, Pascale Jeannin, Jean-François Gauchat, Aline Blaecke, Martine Malissard, Thien N'Guyen, Nathalie Thieblemont, and Yves Delneste From the Centre d'Immunologie Pierre Fabre, Saint-Julien en Genevois, France; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité U564, Centre Hospitalier Universitaire (CHU) Angers; and Centre National de la Recherche Scientifique (CNRS) FRE 2444, Université René Descartes Paris V, Hôpital Necker, Institut Fédératif de Recherche Necker Enfants Malades, Paris, France. Although human CD56+CD3- natural killer (NK) cells participate in 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 on recognition of pathogen-associated molecular patterns (PAMPs). We therefore evaluated whether the 2 bacterial protein PAMPs, the outer membrane protein A from Klebsiella pneumoniae (KpOmpA) and flagellin, which signal through TLR2 and TLR5, respectively, may directly stimulate human NK cells. These proteins induce interferon- (IFN-) production by NK cells and synergize with interleukin-2 (IL-2) and proinflammatory cytokines in PAMP-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 the 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 through TLRs and evidence defensins as a novel and direct cytotoxic pathway involved in NK cell-mediated protection against microorganisms. (Blood. 2004;104:1778-1783) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Iannello, O. Debbeche, S. Samarani, and A. Ahmad Antiviral NK cell responses in HIV infection: I. NK cell receptor genes as determinants of HIV resistance and progression to AIDS J. Leukoc. Biol., July 1, 2008; 84(1): 1 - 26. [Abstract] [Full Text] [PDF] R. M. Craddock, J. 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