1. Immunostimulating capacities of stabilized RNA molecules.
- Author
-
Scheel B, Braedel S, Probst J, Carralot JP, Wagner H, Schild H, Jung G, Rammensee HG, and Pascolo S
- Subjects
- Adaptor Proteins, Signal Transducing, Adjuvants, Immunologic genetics, Adjuvants, Immunologic metabolism, Animals, Antigens, CD immunology, Antigens, CD metabolism, Antigens, Differentiation immunology, Dendritic Cells drug effects, Dendritic Cells metabolism, Enzyme-Linked Immunosorbent Assay, Immunization, Interleukin-12 immunology, Interleukin-12 metabolism, Interleukin-6 immunology, Interleukin-6 metabolism, Lymphocyte Activation drug effects, Lymphocyte Activation immunology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Myeloid Differentiation Factor 88, RNA, Messenger metabolism, RNA, Messenger pharmacology, Receptors, Immunologic immunology, Spleen immunology, Thionucleotides immunology, Thionucleotides pharmacology, Adjuvants, Immunologic pharmacology, Dendritic Cells immunology, RNA, Messenger immunology
- 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.
- Published
- 2004
- Full Text
- View/download PDF