Immunity in humans comprises both reactions that can change during an individual’s life (adaptive immunity) and reactions that occur in a more stereotypic way each time we encounter an infectious agent (innate immunity). Adaptive immunity can be described as the immune memory of the individual whereas innate immunity as the evolutionary memory of a species or population. Insects are perfect model systems to study innate immunity. We use primarily two model insects: a lepidopteran species (Galleria mellonella) and the vinegar fly (Drosophila melanogaster), which is one of the best established model systems in biology. At present our focus is on the following projects:

The coagulation of insect hemolymph

Arthropods with their open circulatory systems seal wounds and keep bacteria from entering the hemocoel using efficient clotting systems. Until some years ago little was known about the molecular basis for clotting of insect hemolymph. We have established a number of methods to study this reaction in Drosophila melanogaster. Using these methods, we could show that during Drosophila clotting, extracellular webs are formed, which immobilize bacteria and prevent their dissemination into the hemocoel (Fig.1). In addition, proteomics studies allowed us to identify several proteins involved in this reaction. Mutants in the genes encoding these proteins show immune defects. Our results contribute to a more complete picture of the function and evolution of innate immunity. In collaboration with Dr. Heiko Herwald (Lund University) we study which implications our findings have for the human immune system.

The insect response against entomopathogenic nematodes

To challenge the fly’s immune system we use different methods including injection of bacteria, wasp infestation but also infection with entomopathogenic nematodes and their associated bacteria. This work involves a close collaboration with the groups of Dr. Pavel Hyrsl (Brno, Czech Republic) and Dr. Michal Zurovec (Ceske Budejovice, Czech Republic). We found that the response against nematodes differs from most previously described immune responses in Drosophila and relies amongst others on the clotting system. Using a genome-wide survey of the transcriptional changes after nematode infections we identified additional factors that are specifically required during the response against nematodes.

The immune response against early stages of tumor development

In this project we study how the innate immune reacts against tumors. For this we also rely on Drosophila melanogaster as a model system. There are a number of mutant fly strains, which develop tumors but we induce a tumorigenic state genetically. We find that both natural- and experimentally-induced tumors activate immune responses and we have characterized this response both at the cellular and humoral level. The cellular response bears many similarities with the granuloma-like encapsulation reaction, which insects mount for example against eggs from parasitoid wasps. A genome-wide transcriptional analysis reveals similarities to the immune response against wasps but also to other infection models. In addition the response against early tumor stages shows its own specific signature for example a recruitment of pathways involved in wound healing.