Two distinct activation states of plasmacytoid dendritic cells induced by influenza virus and CpG 1826 oligonucleotide.
There is growing evidence that plasmacytoid dendritic cells (pDC) are involved in the innate recognition of various microbes. However, the precise consequences of pathogen recognition on pDC activation and function are incompletely understood. Using a novel transgenic mouse model that facilitates the isolation of highly pure pDC populations, we found that influenza virus PR/8, a TLR7 ligand, and CpG 1826 oligonucleotide, a TLR9 ligand, induced surprisingly divergent activation programs in these cells. pDC stimulated with PR/8 produced large amounts of type I IFNs, and CpG 1826-stimulated pDC expressed higher levels of costimulatory molecules and proinflammatory cytokines and induced stronger proliferation of T cells. Transcriptome analysis uncovered the differential regulation in pDC of 178 and 1577 genes by PR/8 and CpG 1826, respectively. These differences may relate to the activation of discrete signaling pathways, as evidenced by distinct ERK1/2 and p38 MAPK phosphorylation kinetics. Finally, pDC isolated ex vivo during PR/8 infection or after i.v. CpG 1826 injection resembled their in vitro counterparts, corroborating that these cells can adopt specialized phenotypes in vivo. Thus, pDC display remarkable functional flexibility, which emphasizes their versatile functions in antimicrobial immunity and inflammatory processes.
Iparraguirre
Amaya
A
Immunology Program, The Wistar Institute, Department of Penn Bioinformatics Core, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Tobias
John W
JW
Hensley
Scott E
SE
Masek
Katherine S
KS
Cavanagh
Lois L
LL
Rendl
Michael
M
Hunter
Christopher A
CA
Ertl
Hildegund C
HC
von Andrian
Ulrich H
UH
Weninger
Wolfgang
W
D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology* / Q000821:virology*; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D018398:Homeodomain Proteins / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D009975:Orthomyxoviridae; D010950:Plasma Cells / Q000187:drug effects / Q000502:physiology / Q000821:virology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014158:Transcription, Genetic / Q000187:drug effects
D015226:Dinucleoside Phosphates; D018398:Homeodomain Proteins; D009838:Oligodeoxyribonucleotides; C064658:RAG-1 protein; C015772:CpG dinucleotide