Bacterial DNA and immunostimulatory CpG oligonucleotides trigger maturation and activation of murine dendritic cells.
Bacterial DNA and immunostimulatory (i.s.) synthetic CpG-oligodeoxynucleotides (ODN) act as adjuvants for Th1 responses and cytotoxic T cell responses to proteinaceous antigens. Dendritic cells (DC) can be referred to as "nature's adjuvant" since they display the unique capacity to sensitize naive T cells. Here, we demonstrate that bacterial DNA or i.s. CpG-ODN cause simultaneous maturation of immature DC and activation of mature DC to produce cytokines. These events are associated with the acquisition of professional antigen-presenting cell (APC) function. Unfractionated murine bone marrow-derived DC and FACS-fractionated MHC class IIlow (termed immature DC) or MHC class IIhigh populations (termed mature DC) were stimulated with bacterial DNA or i.s. CpG-ODN. Similar to lipopolysaccharide, i.s. CpG-ODN caused up-regulation of MHC class II, CD40 and CD86, but not CD80 on immature and mature DC. In parallel both DC subsets were activated to produce large amounts of IL-12, IL-6 and TNF-alpha. CpG-ODN-activated DC displayed professional APC function in allogeneic mixed lymphocyte reaction and in staphylococcal enterotoxin B-driven naive T cell responses. We interpret these findings to mean that bacterial DNA and i.s. CpG-ODN cause maturation (first step) and activation (second step) of DC to bring about conversion of immature DC into professional APC.
Sparwasser
T
T
Institute of Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Germany.
Koch
E S
ES
Vabulas
R M
RM
Heeg
K
K
Lipford
G B
GB
Ellwart
J W
JW
Wagner
H
H
D000276:Adjuvants, Immunologic; D000818:Animals; D001854:Bone Marrow Cells; D019013:CD40 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology*; D004269:DNA, Bacterial / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004790:Enzyme Induction; D005260:Female; D015793:HLA-B7 Antigen / Q000378:metabolism; D006410:Hematopoiesis; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation; D001616:beta-Galactosidase / Q000378:metabolism
D000276:Adjuvants, Immunologic; D019013:CD40 Antigens; D004269:DNA, Bacterial; D015793:HLA-B7 Antigen; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D001616:beta-Galactosidase