International Immunology Advance Access published online on September 18, 2007
International Immunology, doi:10.1093/intimm/dxm073
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Induction of NKG2D ligands on human dendritic cells by TLR ligand stimulation and RNA virus infection
1 Departments of Microbiology and Immunology
2 Department of Pediatrics, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan
3 Department of Immunology, Osaka Medical Center for Cancer, Higashinari-ku, Osaka 537-8511, Japan
4 Present address: Department of Molecular Immunogy, Nara Institute for Science and Technology, Ikoma, Nara 631-0101, Japan
5 Present address: Toei Hospital, Kita-41, Higashi-6, Higashi-ku, Sapporo 007-0841, Japan
Correspondence to: Correspondence to: T. Seya; E-mail: seya-tu{at}med.hokudai.ac.jp
Monocyte-derived dendritic cells (mDCs) and NK cells are reciprocally activate via cytokines and cell–cell contact. Although seven human NKG2D ligands (NKG2DLs), UL16-binding proteins (ULBP) 1, 2, 3 and 4, retinoic acid early transcript 1G (RAET1G) and MHC class I-related chains A and B, have been reported, the differential distribution and roles of these ligands in the maturation of human mDCs have not been elucidated. In the present study, we produced polyclonal antibodies (pAbs) directed against human ULBP1, 2 and 3. All these ULBPs were detected on human mDCs when probed by the pAbs, although their expression profiles were different. We next investigated what kinds of Toll-like receptor agonists and RNA viruses [influenza virus, human respiratory syncytial virus (RSV), measles virus and hepatitis C virus (HCV)] induced the expression of NKG2DLs on mDCs. ULBP1 was up-regulated on mDCs in response to LPS or infection with RSV. The expression of ULBP2 was induced by LPS and poly I:C, indicating that the TIR-containing adapter molecule-1 (TIR domain-containing adaptor-inducing IFN) pathway is associated with ULBP2 induction. Although infection with HCV did not cause up-regulation of NKG2DLs, other RNA virus infections and poly I:C promoted expression of ULBP2 and RAET1G in an IFN-
/ß-independent manner. Finally, the over-expression of ULBP1 and 2 on mDCs facilitated NK cell proliferation and IFN-
production through a mDC–NK cell interaction in the presence of IL-2. Hence, the results reflect the important role of NKG2DLs on human mDCs in mDC-mediated NK cell activation.
Keywords: dendritic cells, human, NK activation, Toll-like receptors, ULBP, viral infection
Transmitting editor: K. Okumura
Received 27 November 2006, accepted 11 June 2007.
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