Kliniken & Institute ... Institute Zentrum für... Medizinische... Forschung Research Eigenbrod

Research Group Eigenbrod

Group Leader:

 

PD Dr. Tatjana Eigenbrod

Research interests

The scientific focus of my research is infection and immunity with special emphasis on RNA-mediated immune activation. Microbial RNA has emerged as a potent activator of innate immune responses that, depending on its subcellular localization, is sensed by either endosomal or cytoplasmic pattern recognition receptors. While the immunostimulatory properties of viral RNA have been studied extensively, bacterial RNA is far less well characterized. We have previously demonstrated that human monocytes and myeloid DCs recognize bacterial RNA via endosomal Toll-like receptor 8 (TLR8), triggering the production of pro-inflammatory cytokines including TNF, IL-6 and IFN-β. By contrast, endosomal TLR13 serves as sensor for bacterial RNA in the murine system. Moreover, we and others have identified a predominant role of RNA sensing by endosomal TLRs in initiating innate immune responses against the skin pathogen Streptococcus pyogenes (S. pyogenes) in both the human and murine system, highlighting the physiological relevance of RNA sensing in defence of infections. Ongoing research of my group further indicates that bacterial RNA within S. pyogenes is crucial for inducing metabolic and epigenetic reprogramming during S. pyogenes infection which is associated with an enhanced immune response against heterologous immune stimuli, a process known as ‘trained immunity’.

Yet, sensing of RNA by endosomal TLRs seems to have a dual role in the skin: While immune activation by bacterial RNA is beneficial in the context of infections with S. pyogenes, misled recognition of self RNA in the skin can be detrimental and trigger autoimmune disorders including psoriasis. To which extend bacterial RNA may contribute to the pathogenesis of psoriasis or aggravate the disease phenotypes has not yet been established and will be investigated as part of the SFB TR156.

Projects

  • SFB TR156, Project B05: Dual implications of RNA mediated immune activation in the skin
  • Bacterial RNA as trigger of trained immunity
  • Metabolic and epigenetic reprogramming during S. pyogenes infection

Lab members

Anna Hafner, MD

Dr. Isabel Freund (Alumni)

Dr. Felix Schmitt (Alumni)

Dr. Katharina Rimbach (Alumni)

Selected Publications

Crucial Role of Nucleic Acid Sensing via Endosomal Toll-Like Receptors for the Defense of Streptococcus pyogenes in vitro and in vivo. Hafner A, Kolbe U, Freund I, Castiglia V, Kovarik P, Poth T, Herster F, Weigand MA, Weber ANR, Dalpke AH, Eigenbrod T. Front Immunol. 2019 Feb 21;10:198

RNA Modifications Modulate Activation of Innate Toll-Like Receptors. Freund I, Eigenbrod T, Helm M, Dalpke AH. Genes (Basel). 2019 Jan 29;10(2).

Double methylation of tRNA-U54 to 2'-O-methylthymidine (Tm) synergistically decreases immune response by Toll-like receptor 7. Keller P, Freund I, Marchand V, Bec G, Huang R, Motorin Y, Eigenbrod T, Dalpke A, Helm M. Nucleic Acids Res. 2018 Oct 12;46(18):9764-9775

Identification of an optimized 2'-O-methylated trinucleotide RNA motif inhibiting Toll-like receptors 7 and 8. Schmitt FCF, Freund I, Weigand MA, Helm M, Dalpke AH, Eigenbrod T. RNA. 2017 Sep;23(9):1344-1351

TLR8 Senses Bacterial RNA in Human Monocytes and Plays a Nonredundant Role for Recognition of Streptococcus pyogenes. Eigenbrod T, Pelka K, Latz E, Kreikemeyer B, Dalpke AH. J Immunol. 2015 Aug 1;195(3):1092-9

Bacterial RNA: An Underestimated Stimulus for Innate Immune Responses. Eigenbrod T, Dalpke AH. J Immunol. 2015 Jul 15;195(2):411-8

2'-O-Methylation within Bacterial RNA Acts as Suppressor of TLR7/TLR8 Activation in Human Innate Immune Cells. Rimbach K, Kaiser S, Helm M, Dalpke AH, Eigenbrod T. J Innate Immun. 2015;7(5):482-93

Cytosolic double-stranded RNA activates the NLRP3 inflammasome via MAVS-induced membrane permeabilization and K+ efflux. Franchi L*, Eigenbrod T*, Muñoz-Planillo R, Ozkurede U, Kim YG, Arindam C, Gale M Jr, Silverman RH, Colonna M, Akira S, Núñez G. J Immunol. 2014 Oct 15;193(8):4214-4222. *authors contributed equally

Bacterial RNA mediates activation of caspase-1 and IL-1β release independently of TLRs 3, 7, 9 and TRIF but is dependent on UNC93B. Eigenbrod T, Franchi L, Muñoz-Planillo R, Kirschning CJ, Freudenberg MA, Núñez G, Dalpke A. J Immunol. 2012 Jul 1;189(1):328-36.

The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Franchi L, Eigenbrod T, Muñoz-Planillo R, Nuñez G. Nat Immunol. 2009 Mar;10(3):241-7