Immunostimulating capacities of stabilized RNA molecules.
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.
Scheel
Birgit
B
CureVac GmbH, Tübingen, Germany.
Braedel
Sybilla
S
Probst
Jochen
J
Carralot
Jean-Philippe
JP
Wagner
Hermann
H
Schild
Hansjorg
H
Jung
Günther
G
Rammensee
Hans-Georg
HG
Pascolo
Steve
S
D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000943:Antigens, Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007114:Immunization; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013873:Thionucleotides / Q000276:immunology / Q000494:pharmacology
D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000943:Antigens, Differentiation; D015850:Interleukin-6; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D013873:Thionucleotides; D018664:Interleukin-12