CpG oligodeoxynucleotides down-regulate macrophage class II MHC antigen processing.
Unmethylated CpG motifs in bacterial DNA or short oligodeoxynucleotides (ODN) stimulate cells of the immune system and provide adjuvant activity. CpG DNA directly activates macrophages to secrete IL-12 and TNF-alpha and increases transcription of various genes, but its effects on macrophage Ag processing remain uncertain. The effects of CpG ODN on class II MHC (MHC-II) Ag processing and presentation were examined using peritoneal macrophages that were cultured for 18 h with CpG ODN and then pulsed with protein Ags. T cell hybridomas were used to detect presentation of specific peptide:MHC-II complexes. Both CpG ODN and LPS inhibited processing of bovine RNase and hen egg lysozyme. Presentation of exogenous peptides was inhibited to a lesser degree. Treatment of macrophages for 18 h with CpG ODN decreased surface MHC-II expression, as measured by flow cytometry. Furthermore, Northern blot analysis revealed that treatment with CpG ODN decreased I-Ak mRNA. Endocytosis by macrophages, as measured by uptake of fluorescent dextran, was not altered by treatment with CpG ODN. The inhibitory effect of CpG ODN on Ag processing was seen after prolonged (18 h) treatment of macrophages, but not after short treatment (e.g., 2 h) with CpG ODN and protein Ag. Enhancement of macrophage Ag processing was not seen at any time point of CpG ODN exposure, in contrast to data from other studies with dendritic cells. In summary, exposure of macrophages to CpG ODN results in a decrease in macrophage Ag processing and presentation, which is largely mediated by a decrease in synthesis of MHC-II molecules.
Department of Pathology, Division of Infectious Diseases, Case Western Reserve University, Cleveland, OH 44106, USA.
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RS
Chu
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Askew
E H
EH
Noss
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Tobian
A M
AM
Krieg
C V
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Harding
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000235:genetics; D018899:CpG Islands / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D004705:Endocytosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D046911:Macromolecular Substances; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D009838:Oligodeoxyribonucleotides / Q000276:immunology* / Q000494:pharmacology; D010452:Peptide Biosynthesis / Q000187:drug effects / Q000276:immunology; D010455:Peptides / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000276:immunology / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D011500:Protein Synthesis Inhibitors