Maturation of murine bone marrow-derived dendritic cells with poly(I:C) produces altered TLR-9 expression and response to CpG DNA.
Although poly(I:C) and LPS induced differential dendritic cell (DC) cytokine profiles and toll-like receptor (TLR) expression, all were capable of causing phenotypic and functional DC maturation. Both LPS and poly(I:C) downregulated TLR-4/MD-2 expression on DCs. Although poly(I:C) highly upregulated their cell surface TLR-9 expression, LPS upregulated the intracellular TLR-9 expression. LPS-treated DCs could not produce IL-12p70 in response to subsequent both LPS- and CpG DNA-stimulation. On the other hand, poly(I:C)-treated DCs retained to produce IL-12p70 by subsequent CpG DNA-stimulation, while subsequent LPS-stimulation did not induce IL-12p70 production. Chloroquine, inhibitor of endosomal maturation, completely inhibited cytokine production of LPS-treated DCs as well as unstimulated control in response to subsequent CpG DNA-stimulation, while it failed to delete the IL-12p40 and IL-10 production in poly(I:C)-treated DCs. These data suggest that poly(I:C) may induce a novel DC phenotype that preserves the capacity of cytokine production to subsequent CpG DNA-stimulation.
Tsujimoto
Hironori
H
Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610, USA. tsujiflorida@aol.com
Efron
Philip A
PA
Matsumoto
Tadashi
T
Ungaro
Ricardo F
RF
Abouhamze
Amer
A
Ono
Satoshi
S
Mochizuki
Hidetaka
H
Moldawer
Lyle L
LL
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation; D002738:Chloroquine / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
C408982:CPG-oligonucleotide; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D016753:Interleukin-10; D018664:Interleukin-12; D002738:Chloroquine; D011070:Poly I-C