Abstract
Since direct injection of naked mRNA induces an immune response, we tested the capacity of RNA to signal danger. We show here that mRNA molecules that are protected from immediate degradation either through interaction with cationic proteins (trans protection) or through chemical modification of the phosphodiester backbone (phosphorothioate RNA; cis protection) act as sequence-independent danger signals on mouse DC. As opposed to CpG DNA, the cis-stabilized RNA is degraded in a few minutes, does not activate B cells and, in contrast to double-stranded RNA, requires MyD88 for activation of the DC. We postulate that phosphorothioate RNA, which mimics trans-stabilized RNA, is a new PAMP.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adjuvants, Immunologic / genetics
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Adjuvants, Immunologic / metabolism
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Adjuvants, Immunologic / pharmacology*
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Animals
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Antigens, CD / immunology
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Antigens, CD / metabolism
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Antigens, Differentiation / immunology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Enzyme-Linked Immunosorbent Assay
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Immunization
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Interleukin-12 / immunology
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Interleukin-12 / metabolism
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Interleukin-6 / immunology
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Interleukin-6 / metabolism
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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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Mice, Inbred C57BL
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Mice, Knockout
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Myeloid Differentiation Factor 88
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RNA, Messenger / immunology*
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RNA, Messenger / metabolism
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RNA, Messenger / pharmacology
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Receptors, Immunologic / immunology
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Spleen / immunology
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Thionucleotides / immunology
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Thionucleotides / pharmacology
Substances
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Adaptor Proteins, Signal Transducing
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Adjuvants, Immunologic
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Antigens, CD
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Antigens, Differentiation
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Interleukin-6
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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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RNA, Messenger
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Receptors, Immunologic
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Thionucleotides
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Interleukin-12