Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class I MHC.
Plasmacytoid dendritic cells (pDCs) are an important source of type I interferon (IFN) during initial immune responses to viral infections. In mice, pDCs are uniquely characterized by high-level expression of Ly49Q, a C-type lectin-like receptor specific for class I major histocompatibility complex (MHC) molecules. Despite having a cytoplasmic immunoreceptor tyrosine-based inhibitory motif, Ly49Q was found to enhance pDC function in vitro, as pDC cytokine production in response to the Toll-like receptor (TLR) 9 agonist CpG-oligonucleotide (ODN) could be blocked using soluble monoclonal antibody (mAb) to Ly49Q or H-2K(b). Conversely, CpG-ODN-dependent IFN-alpha production by pDCs was greatly augmented upon receptor cross-linking using immobilized anti-Ly49Q mAb or recombinant H-2K(b) ligand. Accordingly, Ly49Q-deficient pDCs displayed a severely reduced capacity to produce cytokines in response to TLR7 and TLR9 stimulation both in vitro and in vivo. Finally, TLR9-dependent antiviral responses were compromised in Ly49Q-null mice infected with mouse cytomegalovirus. Thus, class I MHC recognition by Ly49Q on pDCs is necessary for optimal activation of innate immune responses in vivo.
Tai
Lee-Hwa
LH
Laboratory of Molecular Immunology, Clinical Research Institute of Montréal, Montréal, Quebec, Canada.
Goulet
Marie-Line
ML
Belanger
Simon
S
Toyama-Sorimachi
Noriko
N
Fodil-Cornu
Nassima
N
Vidal
Silvia M
SM
Troke
Angela D
AD
McVicar
Daniel W
DW
Makrigiannis
Andrew P
AP
D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology*; D006566:Herpesviridae Infections / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000235:genetics / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology
C408982:CPG-oligonucleotide; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; C527089:Klra17 protein, mouse; D055650:NK Cell Lectin-Like Receptor Subfamily A; D009838:Oligodeoxyribonucleotides; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9