Current page: IMMEI › Institute of Experimental Immunology

Institute of Experimental Immunology

1. Research overview
2. Research topics
3. Group members
4. Grant support
5. Principal investigator
6. Publications
 

Research overview

Our common interests are the mechanisms governing antigen-presentation and the ensuing immune response in the defense against infections and in immune-mediated disease. We focus at 3 major topics:
1.) Mechanisms of antigen cross-presentation to cytotoxic CD8 T cells
2.) Peripheral immune tolerance of T and B lymphocytes against self antigens
3.) Role of dendritic cells in diseases, especially in the kidney disease

T lymphocytes (=T cells) defend our body against infections with microbes. They require activation by antigen-presenting cells, in particular dendritic cells (DCs). These DCs collect antigens in various tissues, migrate to draining lymph nodes, and activate the T cells there. The mechanism of cross-presentation enables DCs to activate the CD8+ cytotoxic T cells, which are crucial for the immune defense against viruses, some intracellular bacteriae and tumors (Figure on the right).

We have previously shown that DCs can destroy harmful cytotoxic T cells, and thereby prevent them from damaging our own body. In case of failure of this form of peripheral immune tolerance, which is also known as cross-tolerance, autoimmune diseases arise, such as type I diabetes mellitus or multiple sclerosis (Figure on the left shows common autoimmune diseases). Other forms of peripheral immune tolerance include the induction of regulatory T cells, which can suppress harmful T cells. We are interested in suppression of harmful B cells, and prevention of autoantibody formation, which play important roles in various autoimmune diseases such as glomerulonephritis or rheumatoid arthritis.

 

Our third topic of interest is the role of dendritic cells and other myeloid cells in local immune responses in non-lymphoid tissues, with a special emphasis on the kidney dendritic cells. Here we wish to understand the immune mechanisms underlying diseases such responses as glomerulonephritis and cystitis/pyelonephritis. Furthermore, we study DC's in the eye, the intestine and the heart.

 

 

Research topics
 

Role of Chemokines in Cross-presentation (SFB704)

Verena Semmling, Katharina Hochheiser, Annkristin Heine, Elisabeth Mettke; Previous: V. Lukacs-Kornek, Christoph Thaiss 

Chemokines regulate migration and encounters of immune cells. In cross-presentation, various rare immune cells have to meet. Using various knockout mice we study which chemokine receptors are instrumental in orchestrating their migratory behavior in vivo. In collaboration with Waldemar Kolanus and Irmgard Förster we have recently discovered an alternative way of cross-priming that involves NKT cells, the chemokine CCL17 and its chemokine receptor CCR4 (Semmling et al, Nat Immunol 2010).
 

Cell-biology of Cross-presentation (SFB645)

Lars Franken, Catherine Gottschalk, Lukas Heineck; previous: S. Burgdorf, Achmet Imam-Chasan, M. Weimershaus, V. Böhnert

Together with Dr. Sven Burgdorf's group (now professor at the LIMES institute Bonn), we investigate the cell biological mechanisms underlying cross-presentation. We have recently demonstrated that antigens intended for presentation on MHC I or MHC II molecules are internalized by distinct endocytosis mechanisms and targeted into different organelles. Whilst pinocytosis and scavenger receptor-mediated endocytosis introduce antigens into lysosomes for presentation exclusively on MHC II molecules, the mannose receptor routed the antigen into early endosomes, from which it was processed only for presentation on MHC I. After internalization, mannose-receptor-endocytosed antigens were transported out of the endosomes into the cytoplasm for degradation. The resulting peptides were transported back into the same endosomes by TAP, a molecule from the ER, which is recruited to endosomes in a TLR4- and MyD88-dependent fashion. In these endosomes, the antigenic peptides were subsequently loaded on MHC I molecules and transported to the cell membrane for presentation to T cells (Burgdorf et al, Science 2007, Nat Immunol 2008). Current projects mainly focus on the characterization of the endosomes dedicated to cross-presentation, the export of antigens into the cytoplasm and the influence of antigen modifications and cell type on antigen presentation.
 

Peripheral B cell tolerance

Isis Ludwig-Protugall, Janine Gotot, Sonny Leopold, Melanie Eichler;  Previous: Vera Damuzzo, Cathrin Conradt

We are interested in mechanisms of peripheral B cell tolerance against non-lymphatic tissue autoantigens and prevention of autoantibody generation. To study this question, we have generated novel transgenic mice, which allow tracking the response and fate of autoreactive B cells in vivo. Our findings demonstrate that regulatory T cells control autoreactive B cells by blocking their response to autoantigen and by inducing their apoptosis in the autoantigen-draining lymph node and in the spleen (Ludwig-Portugall, J Immunol 2008, Eur J Immunol 2009).
 

Immune reactions in urinary tract infections

Daniel R. Engel, André Tittel, Marzena Schiwon, Sebastian Gutweiler, Chrystel Llanto, Christoph Heuser, Simon Teteris; Previous: C. Weisheit

Urinary tract infections are among the most common infections, and are usually due to uropathogenic E. coli bacteriae (UPEC) ascending entering the urethra. UPEC can enter uroepithelial cells, to hide there from immune survey and to reemerge in situations of reduced immune defense. We have developed an animal model that allows studying the underlying immune mechanisms and the consequences for kidney function in detail (Engel et al, J Immunol 2008, Tittel et al, JASN 2011).
 

 

Role of dendritic cells in immune regulation in non-lymphatic tissues

 Daniel R. Engel, André Tittel, Marzena Schiwon, Sebastian Gutweiler, Thorsten Urcyniczok, Martin Otte, Florian Hoß; Previous: V. Lukacs-Kornek, E. Hamilton-Williams, F. Heymann, J. Scholz, Anne F. Alex

1a.    In the healthy kidney:

The kidney constitutively filtrates and concentrates protein below albumin molecular weight. Enriched filtrated antigen is transported cell-independently within two minutes to renal lymph nodes, where they are taken up by resident dendritic cells by mannose-receptor-mediated endocytosis. Such DCs then tolerized specific CD8+ T cells by inducing apoptosis. These findings identify a constitutively active T cell cross-tolerance mechanism, which is independent of steady-state DC migration. It may contribute to preventing unwanted immunity against innocuous circulating proteins (Lukacs-Kornek, J Immunol 2008).

1b.    In glomerulonephritis:

Glomerulonephritis (GN) is one of the major causes for terminal kidney failure and the need to undergo hemodialysis. Our particular focus is the immunobiology of renal dendritic cells (DC), which form a constitutive tubulointerstitial network, whose function remains to be clarified. We have recently shown that these cells possess a protective role in crescentic GN, but may undergo funtional changes in chronic inflammation, and drive rather than attenuate disease progression (Scholz et al, JASN 2008; Heymann et al, J Clin Invest 2009; Hochheiser et al, JASN 2011). We are interested in the precise underlying mechanisms, including those recruiting DCs into inflamed kidney tissue, the ensuing immune response and in consequences for kidney function and fibrosis. To this end, we employ novel transgenic models that allow dissecting immunity directed against kidney tissue.

1c.    In pyelonephritis:

Little is known about the role of DCs in pyelonephritis, which is also a frequent cause for terminal kidney failure and the need to undergo hemodialysis. We have recently shown that renal DCs act as kidney-resident sentinels that rapidly alerts the immune system to invading bacteria (Tiitel et al, JASN 2011).

2.    In the intestine:

Intestinal manipulation during abdominal surgery frequently leads to postoperative ileus, causing prolonged morbidity. The clinically leading problem is that the entire intestinal tract, and not only the surgically manipulated areas become paralyzed. In a collaboration with Prof. Dr. Jörg Kalff from the Department of Surgery,  University of Bonn Medical Center (KFO115), we have recently found that this is an immune-mediated disease, where resident dendritic cells sense the intestinal trauma and activate Th1 memory T cells, which then disseminate paralysis over the entire intestinal tract (Engel et al, Nat Med 2011).

3.    In the eye:

Age-dependent macula degeneration is the most prevalent cause of blindness in old age. It is believed to result from persisting inflammatory processes at the retina/choroid, and a role of DCs has been proposed. We are aiming at identifying the exact nature of this role, and explore opportunities for therapeutical interventions in a collabopration with Prof. Dr. Nicole Eter from Dept. of Ophthalmology of the University of Münster.

4.    In the heart:

In sepsis, the heart function drastically declines, and increases the risk of complications in intensive care patients. We are exploring the role of heart-resident DCs in this condition in a collaboration with PD Dr. Georg Baumgarten from the Department for Anesthesiology, University clinic of Bonn University.

 

Group Members May 2011

stehend hintere Reihe: André Tittel, Florian Hoß, Christina Ohliger, Christian Kurts, Martin Otte, Annkristin Heine, Simon Teteris

stehend vordere Reihe: Sophie Schonauer, Melanie Eichler, Jessica Gonyer, Chrystel Llanto, Janine Gotot, Catherine Gottschalk, Isis Ludwig-Portugall, Katharina Hochheiser, Lars Franken, Marzena Schiwon, Theodore Peng

knieend: Cathrin Conradt, Albert Job,Christoph Heuser, Sebastian Gutweiler, Christine Weisheit, Verena Semmling, Lucie Delforge  Daniel Engel

Not in picture: Torsten Urcyniczok, Sonny Leopold

 

Grant support

  • German Research Foundation (Deutsche Forschungsgemeinschaft, DFG)

  • Sonderforschungsbereich 704

  • Sonderforschungsbereich 645

  • Sonderforschungsbereich TR57

  • KFO 115

  • KFO 228

  • EU FP7 project INTRICATE

  • DAAD Go8 student exchange with Australia

  • German National Academic Foundation (Studienstiftung des Deutschen Volkes)

  • Bonfor

 

Principal Investigator

Institutes of Molecular Medicine and Experimental Immunology (IMMEI)

University Clinic of Bonn
Sigmund-Freud-Str. 25
D-53105 Bonn, Germany

Tel: +49-(0) 228-287 11050
Fax: +49-(0) 228-287 11052
ckurts{at}uni-bonn.de

 

1985-91       Studies in physics and medicine, University of Göttingen Germany
1986-91       Fellowship German National Academic Foundation
11/1991       Doctoral thesis at the Department of Immunology (Prof. Dr. O. Götze), University of Göttingen
11/91-4/95   Medical Officer and Research Fellow, Department of Nephrology (Prof. Dr. KM Koch), University of Hannover, Germany
4/95-3/98     Postdoctoral Research Fellow, Thymus Biology Unit (Prof. J. Miller) and Immunology Division (Dr. W.R. Heath),
                    The Walter and Eliza Hall Institute for Medical Research (WEHI), Melbourne Australia
4/98-8/00     Medical Officer and Research Fellow, Department of Nephrology, Hannover
6/1999         Lectureship (Habilitation) for Experimental Nephrology
12/1999       Sir Hans Krebs award for basic medical research
8/2000         Board Certification in general internal medicine (Facharzt)
9/2000         Heisenberg-Fellowship of the deutsche Forschungsgemeinschaft
3/00-2/05    Recipient of a career development grant of the German state of Northrhine-Westphalia
9/00-3/03    Assistant Professor, Dpt. of Nephrology and Clinical Immunology (Prof. Dr. J Floege), University of Aachen
9/02-12/02  Visiting scientist, La Jolla Institute for Allergy and Immunology, San Diego USA
04/2003       Full Professor of Molecular Immunology, Institute for Molecular Medicine and Experimental Immunology, University of Bonn
4/2005         Student Mentor of the German National Academic Foundation (Studienstiftung des Deutschen Volkes)
10/2005       Board Certification for Clinical Nephrology (Innere Medizin Teilgebiet Nephrologie)
04/2009       Director Institute of Experimental Immunology, University of Bonn
06/2010       Hans-U.-Zollinger Award of the German Society for Nephrology
12/2011       Gottfried-Wilhelm-Leibniz-Prize of the DFG

 

12 Selected Publications

  1. Tittel AP, Heuser C, Ohliger C, Knolle P, Engel DR, Kurts C. 2011. Kidney dendritic cells rapidly induce innate immunity against bacterial pyelonephritis. J Am Soc Nephrol, 22: 1435-41

  2. Hochheiser K, Engel DR, Hammerich L, Heymann F, Knolle PA, Panzer U, Kurts C. 2011. Kidney dendritic cells become pathogenic during nephrotoxic nephritis with proteinuria. J Am Soc Nephrol, 22(2):306-16

  3. Engel DR, Koscielny A, Wehner S, Maurer J, Schiwon M, Schumak B, Limmer A, Sparwasser T, Hirner A, Knolle PA, Kalff JC, Kurts C. 2010. Th1 memory cells disseminate postoperative ileus over the entire intestinal tract. Nature Medicine, 16(12), 1407-13
    Press release: http://www3.uni-bonn.de/Pressemitteilungen/306-2010

  4. Kurts, C, Robinson BWS, Knolle PA. 2010. Cross-priming in Health and Disease. Nature Rev Immunol, 10(6): 403-414

  5. Semmling V, Lukacs-Kornek V, Thaiss CA, Quast T, Hochheiser K, Panzer U, Rossjohn J, Perlmutter P, Cao J, Godfrey DI, Savage PB, Knolle PA, Kolanus W, Förster I, Kurts C. Alternative cross-priming through CCL17-CCR4-mediated attraction of CTLs toward NKT cell-licensed DCs. Nature Immunol. 2010 Apr;11(4):313-20.
    Press release: http://http://www.kompetenznetze.de/service/nachrichten/2010/six-eye-principle-protects-the-body-from-autoimmune-diseases

  6. Heymann F, Meyer-Schwesinger C, Hamilton-Williams EE, Hammerich L, Panzer U, Kaden S, Floege J, Gröne HJ, Kurts C. 2009. Kidney dendritic cell activation is required for progression of renal disease in a mouse model of glomerular injury. J Clin Invest, 119:1286-97; Epub April 20, 2009 
    Press release: http://bonner-presseblog.de/2009/04/20/bonn-wenn-das-immunsystem-die-eigenen-nieren-bekämpft/

  7. Ludwig-Portugall I, Hamilton-Williams EE, Gotot J, Kurts C. 2009. CD25+ regulatory T cells specifically suppress auto-antibody generation against pancreatic tissue autoantigens. Eur J Immunol, 2009 7:39:225-233

  8. Burgdorf S, Schölz C, Kautz A, Tampé R, Kurts C. 2008. Spatial and mechanistic separation of cross-presentation and endogenous antigen presentation.
    Nature Immunol, 9: 558-566, Epub Mar 30, doi:10.1038/ni.1601 (Comment in Nature Immunol 9: 461-463 & Nature Rev Immunol, Research Highlights 8)
    Press release: http://www3.uni-bonn.de/Pressemitteilungen/wie-killerzellen-auf-die-richtige-spur-kommen

  9. Burgdorf S, Kautz A, Böhnert V, Knolle PA, Kurts C. 2007. Distinct antigen uptake and intracellular routing mechanisms in CD4 and CD8 T cell activation. Science, 316: 612-6
    press release: http://www3.uni-bonn.de/Pressemitteilungen/vergiften-verdauen-oder-in-den-selbstmord-treiben

  10. Kruger T, Benke D, Eitner F, Lang A, Wirtz M, Hamilton-Williams EE, Engel D, Giese B, Muller-Newen G, Floege J, Kurts C. 2004. Identification and functional characterization of dendritic cells in the healthy murine kidney and in experimental glomerulonephritis. J Am Soc Nephrol, 15: 613-21

  11. Kurts C, H Kosaka, FR Carbone, JFAP Miller und WR Heath. 1997. Exogenous class I-restricted cross-presentation of self antigens can lead to deletion of autoreactive CD8+ T cells. J Exp Med, 186: 239-245

  12. Kurts C, WR Heath, FR Carbone, J Allison, JFAP Miller,  H Kosaka. 1996. Constitutive class I-restricted exogenous presentation of self antigens in vivo. J Exp Med, 184: 923-930

Copyright © IMMEI | Credits | Coinlex Webdesign