Save the Date - 10th February 2026 - 3 p.m. - HS20  [15.01.26]

Prof. Dr. Bernd Lepenies

Ludwig-Maximilians-University Munich
Department of Veterinary Sciences
Chair of Biochemistry and Chemistry

Myeloid C-type lectin receptors as targets for immune modulation
Lectin-glycan interactions play a crucial role in the immune system. An important class of lectins in innate immunity
is myeloid C-type lectin receptors (CLRs). CLRs act as pattern recognition receptors and are mainly expressed by
myeloid cells, such as macrophages, dendritic cells, and neutrophils. In innate immunity, CLRs contribute to
self−/non−self discrimination. While recognition of pathogen-associated molecular patterns by CLRs contribute to a
protective immune response on the one hand, CLR engagement can also be exploited by pathogens for immune
evasion on the other hand. Since CLRs often function as endocytic receptors and trigger distinct signaling pathways
in myeloid cells, CLR targeting has proven useful for cell-specific targeting and immune modulation. As examples of
recent findings related to myeloid CLRs, we showed that CLRs affect the severity of infectious diseases and
inflammatory processes. For instance, we identified the CLR CLEC12A as innate sensor of plasmodial hemozoin and
found a crucial role for CLEC12A in the induction of cerebral malaria. In addition, we determined the role of the CLR
Mincle in the recognition of bacteria, including microbiota but also pathogens, such as Legionella pneumophila.

To identify novel CLR/pathogen interactions, we generated CLR libraries in the format of CLR-hFc fusion proteins.
Such CLR-hFc fusion proteins consist of the extracellular domain of a respective CLR containing the carbohydraterecognition
domain, fused to the Fc fragment of human IgG1 molecules. CLR-hFc libraries are available for mice and
men, but we have extended them to large animals and mosquitos as well. Indeed, CLR-hFc fusion proteins have
proven useful to identify CLR ligands from bacteria, viruses, parasites, and self-antigens. Currently, we investigate
CLR functions in veterinary species to exploit them for cell-specific targeting and immune modulation. The
comparison of CLR functions in distinct species may help to unravel the coevolution of pathogens with their
vector/mammalian hosts, thus contributing to the One Health approach.

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