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The Infection Immunology group led by Prof. Dr. Bernd Lepenies focuses on the role of a family of pattern recognition receptors, the so-called C-type lectin receptors (CLRs), in innate immunity. The labs of the Infection Immunology are located at the Research Center for Emerging Infections and Zoonoses (RIZ).

 

C-Type Lectin Receptors (CLRs)

In our immune system, there are different classes of carbohydrate-binding receptors (so-called lectins) that recognize specific carbohydrate structures on glycoproteins and glycolipids, but also other structures like crystals or proteins. C-type lectin receptors (CLRs) represent a large lectin receptor superfamily predominantly expressed by cells of the innate immune system. They recognize conserved glycan structures on pathogens and play a crucial role in the initiation of immune responses. Most, but not all, CLRs bind their ligands in a Ca2+-dependent manner, indicated by the “C” in the name “C”-type lectins. The CLR superfamily is divided into 17 subgroups of membrane bound or secreted receptors. Antigen presenting cells, like dendritic cells or macrophages, mostly express membrane bound myeloid CLRs. Thus, myeloid CLRs are important for immune responses as well as attractive candidates for cell targeting and antigen delivery.

For more information, please see for example Mayer et al., 2017 and Ebbecke et al., 2021.

 

CLR libraries

In our group, the function of CLRs is investigated via several different models. One of our core expertises is the screening and identification of novel interactions between CLRs and either whole pathogens or individual ligands. Key components of these screenings are our CLR libraries (so called CLR-Fc fusion proteins) of different species, as they allow for easy detection in various different assays. These assays include ELISA-, flow cytometry-, fluorescence microscopy- and immunoblot-based binding studies as well as immunoprecipitation and glycan arrays.

For more information, please see for example Johannssen et al., 2015 and Mayer et al., 2018.

Schematische Darstellung eines CLR-Fc Fusionsproteins.

 

CLR-reporter cells and knockout systems

CLR-reporter cells present a cell-based test system to further identify whether binding leads to intracellular signal transduction and is thus capable of initiating innate immune responses. Thus, activation of the cells via the CLR and subsequent intracellular signaling can be visualized and analyzed to serve as an indicator for the binding of a ligand to the respective CLR. Additionally, CLR-/- knockout systems are employed to pinpoint individual effects of single CLRs in comparison to their wildtype counterparts in more complex scenarios.

For more information, please see for example Raulf et al., 2019.

 

This concept is further employed to identify interactions of CLRs with pathogens that include bacteria, viruses, parasites as well as fungi. Using these tools, we intend to identify novel pathogen-derived ligands of CLRs. This knowledge may also further be utilized to target specific antigen-presenting cells via their CLRs. Finally, we aim to get a deeper understanding of how CLRs influence inflammatory processes in vivo.
 

In conclusion, we address the following topics in our research:

  • Identificitaion of novel CLR ligands on pathogens via binding studies
  • Targeting of CLRs on antigen-presenting cells using glycoconjugate ligands
  • Investigation of CLR functions in murine models of infection and autoimmunity

 

 

Contact

University of Veterinary Medicine Hannover
Institute for Immunology

Bünteweg 17, Building 231
30559 Hannover
Tel.: +49 511 953-7920
Fax: +49 511 953-7929
Institute for Immunology

Location map

Route description

GPS-address: Bünteweg 17, 30559 Hannover
Access via building 229 "Institute for Pathology"