Benutzerspezifische Werkzeuge

Projekt 1

Immunostimulation by nucleic acids                


Cells of the innate immune system recognize conserved microbial structures, so called pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors. Among these receptors Toll-like receptors (TLR) 3, -7, -8, -9 and -13 recognize nucleic acids of viral, bacterial or synthetic origin. However, the exact mechanisms of nucleic acid recognition and the differentiation between foreign (dangerous) and self (usually harmless) are still only known partially. Work of our own could show that bacterial RNA represents a PAMP recognized by various immune cells. We could also show that former orphan TLR13 is a murine receptor for bacterial RNA. Posttranscriptional RNA modifications play a decisive role for self/non-self discrimination. We identified 2’O-methylation as a modification that inhibits TLR7 and 8 stimulation. Recent research indicates that also RNA processing is a prerequisite and critical for RNA-TLR interaction; we study how RNA modifications and RNA degradation act together.

Selected publications

Hafner A, Kolbe U, Freund I, Castiglia V, Kovarik P, Poth P, Herster F, Weigand MA, Weber AN, Dalpke AH and Eigenbrod T (2019): Crucial role of nucleic acid sensing via endosomal Toll-like receptors for the defense of Streptococcus pyogenes in vitro and in vivo. Front Immunol, 10:198.doi: 10.3389/fimmu.2019.00198

Keller P, Freund I, Marchand V, Bec G, Huang R, Motorin Y, Eigenbrod T, Dalpke A, Helm M (2018): Double methylation of tRNA-U54 to 2'-O-methylthymidine (Tm) synergistically decreases immune response by Toll-like receptor 7. Nucleic Acids Res. 46(18):9764-9775

Eigenbrod T and Dalpke AH (2015): Bacterial RNA: An Underestimated Stimulus for Innate Immune Responses. J Immunol 195(2): 411-8

Eigenbrod T, Pelka K, Latz E, Kreikemeyer B and Dalpke AH (2015): TLR8 Senses Bacterial RNA in Human Monocytes and Plays a Nonredundant Role for Recognition of Streptococcus pyogenes. J Immunol 195(3):1092-9

Hidmark, A., A. von Saint Paul, A.H. Dalpke (2012): Cutting Edge: TLR13 is a receptor for bacterial RNA. J Immunol 189(6): 2717-2721

Gehrig, S., M.E. Eberle,F. Botschen, K. Rimbach, F. Eberle, T. Eigenbrod, S. Kaiser, W.M. Holmes, V.A. Erdmann, M. Sprinzl, G. Bec, G. Keith, A.H. Dalpke*, M. Helm* (2012): Identification of modifications in microbial, native tRNA that suppress immunostimulatory activity. J Exp Med 209(2): 225-233 *equal contribution