TLR9 cooperates with TLR4 to increase IL-12 release by murine dendritic cells.
Toll-like receptors (TLR) are expressed on the surface or intracellularly by dendritic cells (DC) and recognize specifically different pathogen-associated molecular patterns (PAMPs). Increasing evidence suggests that TLR expressed by DC can cooperate to synergize their functions. Here, we describe the cooperation of TLR9 and TLR4 triggering of murine bone marrow derived DC by CpG oligonucleotides and LPS, respectively. The simultaneous DC stimulation of LPS and CpG showed additive effects on the production of IL-12 but not on other cytokines, such as TNF, IL-6 or IL-10. CpG pretreatment before LPS induced five times more IL-12p40 and IL-12p70 production by DC, whereas LPS pretreatment before CpG showed no effect. The optimal time interval between CpG and LPS treatment was 4h and the synergistic effects were dependent on myeloid differentiation factor 88 (MyD88) but independent from the DNA backbone and did not mediate by nucleosome remodeling. The stimulatory effect could be further enhanced by addition of IFN-gamma but not anti-CD40 antibodies. These data show, that TLR4 and TLR9 can cooperate to increase selectively IL-12 production by DC.
Theiner
Gabi
G
Department of Dermatology, University Hospital Erlangen, Germany.
Rössner
Susanne
S
Dalpke
Alexander
A
Bode
Konrad
K
Berger
Thomas
T
Gessner
André
A
Lutz
Manfred B
MB
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D019013:CD40 Antigens / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
D019013:CD40 Antigens; C408982:CPG-oligonucleotide; D003432:Cross-Linking Reagents; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D009707:Nucleosomes; D009838:Oligodeoxyribonucleotides; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D018664:Interleukin-12; D007371:Interferon-gamma