Activation of plasmacytoid dendritic cells with TLR9 agonists initiates invariant NKT cell-mediated cross-talk with myeloid dendritic cells.
CD1d-restricted invariant NK T (iNKT) cells and dendritic cells (DCs) have been shown to play crucial roles in various types of immune responses, including TLR9-dependent antiviral responses initiated by plasmacytoid DCs (pDCs). However, the mechanism by which this occurs is enigmatic because TLRs are absent in iNKT cells and human pDCs do not express CD1d. To explore this process, pDCs were activated with CpG oligodeoxyribonucleotides, which stimulated the secretion of several cytokines such as type I and TNF-alpha. These cytokines and other soluble factors potently induced the expression of activation markers on iNKT cells, selectively enhanced double-negative iNKT cell survival, but did not induce their expansion or production of cytokines. Notably, pDC-derived factors licensed iNKT cells to respond to myeloid DCs: an important downstream cellular target of iNKT cell effector function and a critical contributor to the initiation of adaptive immune responses. This interaction supports the notion that iNKT cells can mediate cross-talk between DC subsets known to express mutually exclusive TLR and cytokine profiles.
Montoya
Carlos J
CJ
Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
Jie
Hyun-Bae
HB
Al-Harthi
Lena
L
Mulder
Candice
C
Patiño
Pablo J
PJ
Rugeles
María T
MT
Krieg
Arthur M
AM
Landay
Alan L
AL
Wilson
S Brian
SB
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D018899:CpG Islands / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D023461:Myeloid Progenitor Cells / Q000276:immunology* / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000819:agonists*
D015415:Biomarkers; C408982:CPG-oligonucleotide; D016207:Cytokines; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D052899:Pore Forming Cytotoxic Proteins; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D054353:Perforin