Kliniken & Institute … Institute Zentrum für… Medizinische… Forschung

Immunostimulation through bacterial nucleic acids

Cells of the innate immune system recognize conserved microbial structures, so called pathogen-associated molecular patterns (PAMPs). This is achieved by specialized receptors with Toll-like receptors representing the most intensively characterized group. Among these receptors TLR-3, -7, -8 and -9 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 allowed establishing a model of CpG-DNA/TLR9 interaction. Two sites within the extracellular domain of TLR-9 interact with the ligand. Recent work centered on immune recognition of bacterial RNA as well as synthetic siRNA. We could show that bacterial RNA represents a PAMP recognized by various immune cells. Posttranscriptional RNA modifications play a decisive role for self/non-self discrimination. Lately, we could show, that former orphan TLR13 is a murine receptor for bacterial RNA. Present work aims to further characterize the modes of bacterial RNA recognition and stimulation. A new project was recently initiated on immunostimulation of professional immune cells by virus RNA transferred from Hepatitis C virus infected cells by means of secreted microvesicles.
[press statement]

Selected publications

  1. Marchand V, Pichot F, Thüring K, Ayadi L, Freund I, Dalpke A, Helm M, Motorin Y (2017): Next-Generation Sequencing (NGS)-based RiboMethSeq protocol for analysis of tRNA 2’-O-Methylation. Biomolecules 7(1). . pii: E13doi: 10.3390/biom7010013
  2. Eigenbrod T and Dalpke AH (2015): Bacterial RNA: An Underestimated Stimulus for Innate Immune Responses. J Immunol 195(2): 411-8
  3. 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 2015 Jun 22. pii: 1403173. [Epub ahead of print]
  4. Rimbach K, Kaiser S, Helm M, Dalpke AH and Eigenbrod T (2015): 2’-O-methylation within bacterial RNA acts as universal suppressor of human innate immune activation. J Innate Immunity 7(5): 482-493
  5. Kaiser, S.*, K. Rimbach*, T. Eigenbrod, A.H. Dalpke, M. Helm (2014): A modified dinucleotide motif specifies tRNA recognition by TLR7. RNA 20: 1351-1355
  6. 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
  7. Eigenbrod, T., L. Franchi, R. Munoz-Planillo, C.J. Kirschning, M.A. Freudenberg, G. Nunez, A. Dalpke (2012): Bacterial RNA Mediates Activation of Caspase-1 and IL-1ß Release Independently of TLRs 3, 7, 9 and TRIF but is Dependent on UNC93B. J Immunol 189(1): 328-336
  8. 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
  9. Peter ME, Kubarenko AV, Weber ANR, Dalpke AH (2009): Identification of an N-terminal recognition site in TLR9 that contributes to CpG-DNA mediated receptor activation. J Immunol 182(12): 7690-7697
  10. Eberle F, Giessler K, Deck C, Heeg K, Peter M, Richert C, Dalpke AH (2008): Modifications in siRNA that separate immunestimulation from RNA interference. J Immunol 180(5): 3229-3237