Sugar-coated cells: how the body recognizes pathogens

How does the body defend itself against infections? This question drives the research of Professor Bernd Lepenies. Since January 2025, he has held the Chair of Biochemistry and Chemistry at LMU’s Faculty of Veterinary Medicine. Lepenies particularly wants to gain a better understanding of how pathogens interact with the immune system: “I investigate the mechanisms by which an animal or human body recognizes unwanted intruders – that is, how it distinguishes between its own and foreign cells.”

Sugar molecules – a neglected class of macromolecules

At the heart of his work are lectins, key regulatory proteins of the immune system, which recognize specific sugar structures on the surface of cells. “Sugars and their interactions with sugar-binding proteins are still extremely underestimated in science,” reckons the biochemist. When it comes to macromolecules, people tend to be familiar with proteins as molecular tools in cells and nucleic acids that make up genetic material.

Complex sugar structures meanwhile have tended to be overlooked, according to Lepenies. And yet they exist on the surface of every cell as a layer of sugar-modified (glycosylated) proteins and lipids known as the glycocalyx. The interplay between lectins and the glycocalyx plays a vital role in fundamental biological processes, such as development, migration, cell division, and reproduction. Equally, it plays an important part in inflammatory processes and the host-pathogen interaction.

Because each organism has its own specific glycosylation, the immune system can use this differential glycosylation to distinguish between self and non-self and thus identify unwanted cells. Moreover, so-called tumor-associated antigens on the cell surface are usually comprised of sugars. “Lectin interactions are highly promising starting points for novel therapies, and not just against infections, but also against autoimmune diseases and cancers.”

Targeted drug delivery

Bernd Lepenies pursues application-oriented approaches in his work, which exploit the functions of lectins for the targeted distribution of drugs in the body. When activated, some lectins lead to endocytosis – uptake into the cell. This happens because when the right sugar binds to the lectin, it unlocks the cell like a key. The sugar and everything bound to it are then internalized into the cell.

“If, for example, we load a liposome – a tiny bubble of lipids – with a cancer drug or an antibiotic, then we can deliver the drug to certain cells in a much more targeted manner via this sugar-lectin recognition,” explains Lepenies. To do this, of course, you need to know which lectins are present on which cell types. “This is one of the things we investigate, both in humans and in animal species that are relevant for veterinary medicine.”

Training the immune system

The second approach pursued by Lepenies’ research group is a relatively novel concept, which involves specifically training of the innate immune system via lectin receptors, so that they respond more sensitively to certain signals, or conversely develop tolerance to them. This could make it possible to train the immune system to deal with certain pathogens or tumor cells, or prevent it from overreacting as in the case of autoimmune diseases.

This is anything but easy: On the surface of pathogens, there are many different complex sugars, which frequently activate several lectins simultaneously. The various signals can synergistically amplify or mutually downregulate each other. “Though these are certainly hard nuts we have to crack, there is huge potential in this field!” says Lepenies.

A biochemist in veterinary medicine

Asked how he came to this specialist field, Bernd Lepenies replies: “I was always interested in the molecular interaction of pathogens with the immune system.” Pursuing a desire to work with pathogens in a biosecurity lab, he decided to study in Hamburg after leaving school. He completed his doctorate on the topic of malarial infection at the Bernhard Nocht Institute for Tropical Medicine and the University of Hamburg. Next, he worked as a postdoc at ETH Zurich, where he had his first professional encounter with sugars.

Having obtained funding for a junior research group by the German Federal Ministry of Education and Research, he moved to the Max Planck Institute of Colloids and Interfaces in Potsdam while completing his habilitation at the Free University of Berlin. “During this period, I laid the foundation for my work today by combining the insights into immunology from my dissertation days with the knowledge about sugar biochemistry and drug targeting from my postdoc days.”

Holistic and interdisciplinary

He kept glycoimmunology as a main research interest when he took up an appointment at the University of Veterinary Medicine Hannover in 2015. He continued there what he had begun in Berlin, but extended it to various animal species. This was in accordance with the One Health concept, a holistic approach, which proposes that human and animal health are closely linked in the context of a healthy environment. This holistic approach influences Lepenies’ research to this day: “The cross-disciplinary aspect and the extension of my research to the animal world fascinated me. We’re one of the few groups that consider lectins so holistically for humans and animal species relevant to veterinary medicine.”

At the beginning of his career, he never would have imagined teaching and performing research at a faculty of veterinary medicine one day. “Over the years I’ve come to realize that you have to be open to unexpected turns of events and the interconnection of various disciplines.” Lepenies wants to pass on this experience to students as liaison professor for the German Academic Scholarship Foundation and to young researchers as a mentor. In his opinion, they too should think outside of the box and not just rigidly follow a prescribed path. “I guess some could call this a lack of stringency or focus, but I think of it as flexibility and openness to other disciplines – and this openness has helped me a lot in my scientific work so far.”