Abstract
Bacterial DNA and synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs stimulate a strong innate immune response. This stimulation can be abrogated by either removing the CpG DNA or adding inhibitory/suppressive motifs. Suppression is dominant over stimulation and is specific for CpG-induced immune responses (having no effect on LPS- or Con A-induced activation). Individual cells noncompetitively internalize both stimulatory and suppressive ODN. Studies using ODN composed of both stimulatory and suppressive motifs indicate that sequence recognition proceeds in a 5'-->3' direction, and that a 5' motif can block recognition of immediately 3' sequences. These findings contribute to our understanding of the immunomodulatory activity of DNA-based products and the rules that govern immune recognition of stimulatory and suppressive motifs.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / metabolism
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Adjuvants, Immunologic / pharmacology*
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Animals
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CpG Islands / immunology*
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DNA / pharmacology*
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Female
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Flow Cytometry
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Immunosuppressive Agents / metabolism
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Immunosuppressive Agents / pharmacology*
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Interferon-gamma / biosynthesis
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Interleukin-12 / biosynthesis
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Interleukin-6 / biosynthesis
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Lymphocyte Activation / drug effects*
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Lymphocyte Activation / immunology
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Mice
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Mice, Inbred BALB C
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Oligodeoxyribonucleotides / metabolism
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Oligodeoxyribonucleotides / pharmacology*
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Spleen / cytology
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Spleen / drug effects
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Spleen / immunology
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Spleen / metabolism
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Suppressor Factors, Immunologic / biosynthesis
Substances
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Adjuvants, Immunologic
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CPG-oligonucleotide
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Immunosuppressive Agents
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Interleukin-6
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Oligodeoxyribonucleotides
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Suppressor Factors, Immunologic
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Interleukin-12
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Interferon-gamma
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DNA