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Interaction of Monocytes with NK Cells upon Toll-Like Receptor-Induced Expression of the NKG2D Ligand MICA¹

Mercedes Kloss^2,*, Patrice Decker^2,, Katrin M. Baltz^*, Tina Baessler^*, Gundram Jung, Hans-Georg Rammensee, Alexander Steinle, Matthias Krusch^3,* and Helmut R. Salih^3,4,*

^* Department of Hematology and Department of Immunology, Eberhard Karls University of Tuebingen, Germany

Reciprocal interactions between NK cells and dendritic cells have been shown to influence activation of NK cells, maturation, or lysis of dendritic cells and subsequent adaptive immune responses. However, little is known about the crosstalk between monocytes and NK cells and the receptors involved in this interaction. We report in this study that human monocytes, upon TLR triggering, up-regulate MHC class I-Related Chain (MIC) A, but not other ligands for the activating immunoreceptor NKG2D like MICB or UL-16 binding proteins 1–3. MICA expression was associated with CD80, MHC class I and MHC class II up-regulation, secretion of proinflammatory cytokines, and apoptosis inhibition, but was not accompanied by release of MIC molecules in soluble form. TLR-induced MICA on the monocyte cell surface was detected by autologous NK cells as revealed by NKG2D down-regulation. Although MICA expression did not render monocytes susceptible for NK cell cytotoxicity, LPS-treated monocytes stimulated IFN- production of activated NK cells which was substantially dependent on MICA-NKG2D interaction. No enhanced NK cell proliferation or cytotoxicity against third-party target cells was observed after stimulation of NK cells with LPS-activated monocytes. Our data indicate that MICA-NKG2D interaction constitutes a mechanism by which monocytes and NK cells as an early source of IFN- may communicate directly during an innate immune response to infections in humans.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from Deutsche Krebshilfe (10-2004-Sa2), the German Research Foundation (SA 1360/2-2), and the IZKF-Nachwuchsgruppe program of the Medical Faculty at Eberhard Karls University Tuebingen (1466-0-0 and 1604-0-0).

² Me.K. and P.D. contributed equally to this work.

³ Ma.K. and H.R.S. share senior authorship.

⁴ Address correspondence and reprint requests to Dr. Helmut R. Salih, Department of Hematology and Oncology, Eberhard Karls University, Tuebingen, Germany. E-mail address: Helmut.Salih{at}med.uni-tuebingen.de

⁵ Abbreviations used in this paper: DC, dendritic cell; AICL, activation-induced C-type lectin; NKG2DL, NKG2D ligand; MIC, MHC class I-related chain; 7-AAD, 7-amino-actinomycin D; TLRL, TLR ligand; ULBP, UL-16 binding protein family.

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