Research Infection Immunology

Group leader Prof. Dr. Bernd Lepenies

The Infection Immunology group focuses on the role of a family of pattern recognition receptors, the so-called C-type lectin receptors, in innate immunity (see Research for more details). Head of the Infection Immunology group is Prof. Dr. Bernd Lepenies who joined the RIZ in July 2015 (see Group Leader and Publications for more information).

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Prof. Dr. Bernd Lepenies

The Infection Immunology group at the RIZ focuses on the role of C-type lectin receptors (CLRs) in infection and inflammation. In our immune system, there are different classes of carbohydrate-binding receptors (so-called lectins) that recognize specific carbohydrate structures on glycoproteins and glycolipids. CLRs represent a large lectin receptor superfamily predominantly expressed by cells of the innate immune system. CLRs recognize conserved glycan structures on pathogens and play a crucial role in the initiation of immune responses.

In our group, the function of CLRs is investigated by using murine models of infection and autoimmunity. We intend to identify novel carbohydrate ligands of CLRs and utilize CLRs to target antigen-presenting cells. Finally, we aim to get a deeper understanding of how CLRs influence inflammatory processes in vivo.

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Specifically, we address the following topics (see figure):
– Identification of novel CLR ligands on pathogens by glycan/glycoprotein array
– Targeting of CLRs on antigen-presenting cells using carbohydrate ligands
– Investigation of CLR functions in animal models of infection and autoimmunity.

Internships, BSc theses, MSc theses

Applications for internship, BSc and MSc theses are always welcome!

The Infection Immunology group focuses on the role of C-type lectin receptors in pathogen recognition and innate immunity (see figure and Research for more details). We employ a variety of methods including molecular biology techniques, biochemical and immunological methods as well as mouse models of infection and autoimmunity.

If you are interested, please contact Prof. Dr. Bernd Lepenies and send your CV and relevant certificates.

Publications

2017:

T. Johannssen, B. Lepenies*: Glycan-based cell targeting to modulate immune responses. Trends Biotechnol. 2017, in press

T.J. Kottom, D.M. Hebrink, P.E. Jenson, M. Wüthrich, H. Wang, B. Klein, S. Yamasaki, B. Lepenies, A.H. Limper*: The Interaction of Pneumocystis with the C-Type Lectin Receptor Mincle Exerts a Significant Role in Host Defense Against Infection. J. Immunol. 2017, in press.

A.V. Kostarnoy*, P.G. Gancheva, B. Lepenies, A.I. Tukhvatulin, A.S Dzharullaeva, N.B. Polyakov, D.A. Grumov, D.A. Egorova, A.Y. Kulibin, M.A. Bobrov, E.A. Malolina, P.A. Zykin, A.I. Soloviev, E. Riabenko, D.V. Maltseva, D.A. Sakharov, A. Tonevitsky, L.V. Verkhovskaya, D.Y. Logunov, B.S. Naroditsky, A.L. Gintsburg: The receptor Mincle promotes skin allergies and is capable of recognizing cholesterol sulfate. Proc. Natl. Acad. Sci. U.S.A. 2017, in press

S. Mayer, M.-K. Raulf, B. Lepenies*: C‑type lectins: their network and roles in pathogen recognition and immunity. Histochem. Cell Biol. 2017, 147(2), 223-37.

C. Gao, R. Fujinawa, T. Yoshida, M. Ueno, F. Ota, Y. Kizuka, T. Hirayama, H. Korekane, S. Kitazume, T. Maeno, K. Ohtsubo, K. Yoshida, Y. Yamaguchi, B. Lepenies, J. Aretz, C. Rademacher, H. Kabata, A. Hegab, P.H. Seeberger, T. Betsuyaku, K. Kida, N. Taniguchi*: A keratan sulfate disaccharide prevents inflammation and the progression of emphysema in murine models. Am. J. Physiol.-Lung Cell. Mol. Physiol. 2017, 312(2), L268-76.

A. Troegeler, I. Mercier, C. Cougoule, D. Pietretti, A. Colom, C. Duval, T.P. Vu Manh, F. Capilla, R. Poincloux, K. Pingris, J. Nigou, J. Rademann, M. Dalod, F.A. Verreck, T. Al Saati, G. Lugo-Villarino, B. Lepenies, D. Hudrisier, O. Neyrolles*: C-type lectin receptor DCIR modulates immunity to tuberculosis by sustaining type I interferon signaling in dendritic cells. Proc. Natl. Acad. Sci. U.S.A. 2017, 114(4), E540-49.

2016:

H. Bavireddi, R.V. Murthy, M. Gade, S. Sangabathuni, P.M. Chaudhari, C. Alex, B. Lepenies, R. Kikkeri*: Understanding carbohydrate–protein interactions using homologous supramolecular chiral Ru(II)-glyconanoclusters. Nanoscale 2016, 8(47), 19696-702.

K. Brzezicka, U. Vogel, S. Serna, T. Johannssen, B. Lepenies*, N.-C. Reichardt*: Influence of core β-1,2-xylosylation on glycoprotein recognition by murine C-type lectin receptors and its impact on dendritic cell targeting. ACS Chem. Biol. 2016, 11(8), 2347-56.

A. Huber, R.S. Kallerup, H. Franzyk, K.S. Korsholm, B. Lepenies, D. Christensen, C. Foged, R. Lang*: Trehalose-diester glycolipids are superior to monoesters in binding to Mincle, activation of macrophages in vitro, and adjuvant activity in vivo. Innate Immun. 2016, 22(6), 405-18.

2015:

C.N. LaRock, S. Döhrmann, J. Todd, R. Corriden, J. Olson, T. Johannssen, B. Lepenies, R.L Gallo, P. Ghosh, V. Nizet*: Group A streptococcal M1 protein sequesters cathelicidin to evade innate immune killing. Cell Host Microbe 2015, 18(4), 471-77.

C.-H. Lai, J. Hütter, C.-W. Hsu, H. Tanaka, S. Varela-Aramburu, L. De Cola, B. Lepenies*, P.H. Seeberger*: Analysis of carbohydrate-carbohydrate interactions using sugar-functionalized silicon nanoparticles for cell imaging. Nano Lett. 2016, 16(1), 807-11

J. Ostrop, K. Jozefowski, S. Zimmermann, K. Hofmann, E. Strasser, B. Lepenies, R. Lang*: Contribution of MINCLE-SYK signaling to activation of primary human antigen-presenting cells by mycobacterial cord factor and the novel adjuvant TDB. J. Immunol. 2015, in press.

E. Zacco, J. Hütter, J.L. Heier, J. Mortier, P.H. Seeberger, B. Lepenies, B. Koksch*: Towards a tailored presentation of ligands: coiled coil-based glycopeptides for ASGPR targeting. ACS Chem. Biol. 2015, in press.

K. Täuber, B. Lepenies, J. Yuan*: Polyvinylpyridinium-type gradient porous membranes – synthesis, actuation and intrinsic cell growth inhibition. Polym. Chem. 2015, in press.

O. Redy-Keisar, K. Huth, U. Vogel, B. Lepenies, P.H. Seeberger, R. Haag, D. Shabat*: Enhancement of fluorescent properties of near-infrared dyes using clickable oligoglycerol dendrons. Org. Biomol. Chem. 2015, 13(16), 4727-32.

Y.L. Lightfoot, K. Selle, T. Yang, Y.J. Goh, B. Sahay, M. Zadeh, J.L. Owen, N. Colliou, E. Li, T. Johannssen, T. Ganguly, B. Lepenies, T.R. Klaenhammer, M. Mohamadzadeh*: C-type lectin receptor SIGNR3-dependent immune regulation by Lactobacillus acidophilus surface layer protein A in colitis. EMBO J. 2015, 34(7), 881-95.

A. Rabes, S. Zimmermann, K. Reppe, R. Lang, P.H. Seeberger, N. Suttorp, M. Witzenrath, B. Lepenies*, B. Opitz*: The C-type lectin receptor Mincle binds to Streptococcus pneumoniae but plays a limited role in the anti-pneumococcal innate immune response. PLOS One 2015, 10(2): e0117022.

2014:

H. Schoenen, A. Huber, N. Sonda, S. Zimmermann, J. Jantsch, B. Lepenies, V. Bronte, R. Lang*: Differential control of Mincle-dependent cord factor recognition and macrophage responses by the transcription factors C/EBPβ and HIF1α. J. Immunol. 2014, 193(7), 3664-75.

J. Hütter, M. Eriksson, T. Johannssen, R. Klopfleisch, D. von Smolinski, A.D. Gruber, P.H. Seeberger, B. Lepenies*: Role of the C-type lectin receptors MCL and DCIR in experimental colitis. PLOS One 2014, 9(7): e103281.

N.M. van Sorge, J.N. Cole, K. Kuipers, A. Henningham, R.K. Aziz, A. Kasirer-Friede, L. Lin, E.T. Berends, M.R. Davies, G. Dougan, F. Zhang, S. Dahesh, L. Shaw, J. Gin, M. Cunningham, J.A. Merriman, J. Hütter, B. Lepenies, S.H.M. Rooijakkers, R. Malley, M.J. Walker, S.J. Shattil, P.M. Schlievert, B. Choudhury, V. Nizet*: Genetics and virulence role of the classical Group A Streptococcus Lancefield antigen. Cell Host Microbe 2014, 15(6), 729-40.

M. Eriksson, S. Serna, M. Maglinao, M.K. Schlegel, P.H. Seeberger, N.C. Reichardt*, B. Lepenies*: Biological evaluation of multivalent Lewis X-MGL-1 interactions. ChemBioChem 2014, 15(6), 844-51.

S.M. Miltsch, P.H. Seeberger, B. Lepenies*: The C-type lectin-like domain containing proteins Clec-39 and Clec-49 are crucial for Caenorhabditis elegans immunity against Serratia marcescens infection. Dev. Comp. Immunol. 2014, 45(1), 67-73.

M. Maglinao, M. Eriksson, M.K. Schlegel, S. Zimmermann, T. Johannssen, S. Götze, P.H. Seeberger, B. Lepenies*: A platform to screen for C-type lectin receptor-binding carbohydrates and their potential for cell-specific targeting and immune modulation. J. Control. Release. 2014, 175, 36-42.

2013:

M. Eriksson, T. Johannssen, D. von Smolinski, A.D. Gruber, P.H. Seeberger, B. Lepenies*: The C-type lectin receptor SIGNR3 binds to fungi present in commensal microbiota and influences immune regulation in experimental colitis. Front. Immunol. 2013, 4, 196.

M. Maglinao, R. Klopfleisch, P. Seeberger, B. Lepenies*: The C-type lectin receptor DCIR is crucial for the development of experimental cerebral malaria. J. Immunol. 2013, 191(5), 2551-59.

K. Shirato, C. Gao, F. Ota, T. Angata, H. Shogomori, K. Ohtsubo, K. Yoshida, B. Lepenies, N. Taniguchi*: Flagellin/Toll-like receptor 5 response was specifically attenuated by keratan sulfate disaccharide via decreased EGFR phosphorylation in normal human bronchial epithelial cells. BBRC 2013, 435(3): 460-65.

N. Karton-Lifshin, U. Vogel, E. Sella, P.H. Seeberger, D. Shabat*, B. Lepenies*: Enzyme mediated nutrient release: glucose-precursor activation by β-galactosidase to induce bacterial growth. Org. Biomol. Chem. 2013, 11(17): 2903-10.

J. Hütter, J.V. Rödig, D. Höper, U. Reichl, P.H. Seeberger, E. Rapp*, B. Lepenies*: Toward animal cell culture-based influenza vaccine design: viral hemagglutinin N-glycosylation markedly impacts immunogenicity. J. Immunol. 2013, 190(1): 220-30.

2012 and earlier:

C.C. Williams, S.H. Thang, T. Hantke, U. Vogel, P.H. Seeberger, J. Tsanaktsidis*, B. Lepenies*: RAFT-derived polymer-drug conjugates: poly(hydroxypropyl methacryl-amide) (HPMA)-7-ethyl-10-hydroxycamptothecin conjugates. ChemMedChem 2012; 7(2): 281-91.

M.K. Schlegel, J. Hütter, M. Eriksson, B. Lepenies, P.H. Seeberger*: Defined presentation of carbohydrates on a duplex DNA scaffold. ChemBioChem 2011; 12(18): 2791-800.

D. Grünstein, M. Maglinao, R. Kikkeri, M. Collot, K. Barylyuk, B. Lepenies, F. Kamena, R. Zenobi, P.H. Seeberger*: Hexameric supramolecular scaffold orients carbohydrates to sense bacteria. J. Am Chem. Soc. 2011; 133(35): 13957-66.

S. Khil’chenko, T. Zaporozhets, N. Shevchenko, T. Zvyagintseva, P.H. Seeberger, B. Lepenies*: Immunostimulatory activity of fucoidan from the brown alga Fucus evanescens: role of sulfates and acetates. J. Carbohydr. Chem. 2011; 30: 291-305.

R. Gentsch, F. Pippig, K. Nilles, P. Theato, R. Kikkeri, M. Maglinao, B. Lepenies, P.H. Seeberger, H.G. Börner*: Modular approach towards bioactive fiber meshes carrying oligosaccharides. Macromolecules 2010; 43(22): 9239-47.

G.J. Bernardes, R. Kikkeri, M. Maglinao, P. Laurino, M. Collot, S.Y. Hong, B. Lepenies, P.H. Seeberger*: Design, synthesis and biological evaluation of carbohydrate-functionalized cyclodextrins and liposomes for hepatocyte-specific targeting. Org. Biomol. Chem. 2010; 8(21): 4987-96.

R. Kikkeri, B. Lepenies, A. Adibekian, P. Laurino, P.H. Seeberger*: In vitro imaging and in vivo liver targeting with carbohydrate capped quantum dots. J. Am. Chem. Soc. 2009; 131(6): 2110-12.

S. Boonyarattanakalin, X. Liu, M. Michieletti, B. Lepenies, P.H Seeberger*: Chemical synthesis of all phosphatidylinositol mannoside (PIM) glycans from Mycobacterium tuberculosis. J. Am. Chem. Soc. 2008; 130(49): 16791-16799.

J.P. Cramer°, B. Lepenies°, F. Kamena, C. Hölscher, M.A. Freudenberg, G.D. Burchard, H. Wagner, C.J. Kirschning, X. Liu, P.H. Seeberger, T. Jacobs*: MyD88/IL-18-dependent pathways rather than TLRs control early parasitaemia in non-lethal Plasmodium yoelii infection. Microbes Infect. 2008; 10(12-13): 1259-65.

B. Lepenies, J.P. Cramer, G.D. Burchard, H. Wagner, C.J. Kirschning, T. Jacobs*: Induction of experimental cerebral malaria is independent of TLR2/4/9. Med. Microbiol. Immunol. 2008; 197(1): 39-44.

B. Lepenies, K. Pfeffer, M.A. Hurchla, T.L. Murphy, K.M. Murphy, J. Oetzel, B. Fleischer, T. Jacobs*: Ligation of B and T lymphocyte attenuator prevents the genesis of experimental cerebral malaria. J. Immunol. 2007; 179(6): 4093-100.

B. Lepenies, I. Gaworski, S. Tartz, J. Langhorne, B. Fleischer, T. Jacobs*: CTLA-4 blockade differentially influences the outcome of non-lethal and lethal Plasmodium yoelii infections. Microbes Infect. 2007; 9(6): 687-94.