Cell type-specific activation of mitogen-activated protein kinases by CpG-DNA controls interleukin-12 release from antigen-presenting cells.
Activation of antigen-presenting cells (APCs) by invariant constituents of pathogens such as lipopolysaccharide (LPS) or bacterial DNA (CpG-DNA) initiates immune responses. We have analyzed the mitogen-activated protein kinase (MAPK) pathways triggered by CpG-DNA and their significance for cytokine production in two subsets of APCs, i.e. macrophages and dendritic cells (DCs). We found that CpG-DNA induced extracellular signal-regulated kinase (ERK) activity in macrophages in a classic MEK-dependent way. This pathway up-regulated tumor necrosis factor production but down-regulated interleukin (IL)-12 production. However, in DCs, which produce large amounts of IL-12, CpG-DNA and LPS failed to induce ERK activity. Consistent with a specific negative regulatory role for ERK in macrophages, chemical activation of this pathway in DCs suppressed CpG-DNA-induced IL-12 production. Overall, these results imply that differential activation of MAP kinase pathways is a basic mechanism by which distinct subsets of innate immune cells regulate their effector functions.
Häcker
H
H
Institute of Medical Microbiology, Technische Universität München, Trogerstrasse 9, D-81675 Munich.
Mischak
H
H
Häcker
G
G
Eser
S
S
Prenzel
N
N
Ullrich
A
A
Wagner
H
H
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D015226:Dinucleoside Phosphates; D005786:Gene Expression Regulation / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D013873:Thionucleotides; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015226:Dinucleoside Phosphates; D018664:Interleukin-12; D008070:Lipopolysaccharides; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D013873:Thionucleotides; D014409:Tumor Necrosis Factor-alpha; C015772:CpG dinucleotide