IMMUNOLOGY

Our research focuses on cellular mechanisms of innate immunity using Drosophila melanogaster as a model organism. Studies on Drosophila contributed to our understanding of innate immunity in general, and uncovered similarities with the mammalian innate immune system. Although Drosophila possesses potent cellular immune responses, mediated by blood cells, the hemocytes, our knowledge on their heterogeneity and development is fragmentary.

The cellular immune response

Microbes, parasites and abnormally developing tissues are invaded and eliminated by blood cells, the hemocytes. These cells are assumed to be developing in the central hematopoietic organ, the lymph gland, and serve as elements of rapid and effective cellular defence mechanisms, i.e. phagocytosis and encapsulation. Morphologically different populations of hemocytes are responsible for these reactions, but due to the lack of molecular markers their origin, functions and lineage relationships are unclear. To study heterogeneity, we identified immunological markers for blood cells. These markers, many of them identified by us recently as transmembrane receptors, help us study the heterogeneity, function and development of hemocytes using immunological and genetic approaches. Using these markers we focus on the cellular events in the immune reactions, in particular the encapsulation reaction.

Research interests:

Definition of molecular markers for hemocyte subsets

Immunological epitopes of hemocyte-specific antigens can be used as markers for the identification of corresponding hemocytes or hemocyte subsets. We recently discovered immunological epitopes on hemocytes showing a cell-type specific expression pattern. These markers define subsets, i.e. the plasmatocytes, the lamellocytes and the crystal cells that have been identified so far by morphological and functional criteria. The newly discovered molecules, however, allow the dissection of morphologically similar populations to developmentally and functionally distinct subsets, e.g. stem cells and immediate precursors for the plasmatocytes and the lamellocytes. Moreover, several antigens have been detected on lamellocytes, which are expressed sequentially during lamellocyte development and may mark distinct stages of differentiation. The expression pattern of these molecules in different hemocyte compartments is now under study.

Definition of hemocyte subsets and compartments

Three major subsets have been identified so far, namely the phagocytic plasmatocytes, the lamellocytes responsible for the encapsulation reaction and the crystal cells involved in melanisation. The use of immunological markers allows the identification and isolation of hemocyte lineages and the different hemocyte compartments during development and following immune induction. Recently we found that sessile hemocytes form a functional compartment in the larva. The analysis of this compartment, as a niche for blood cell development, is in progress.

Hemocyte-specific molecules involved in the regulation of hemocyte development

In collaboration with Dan Hultmark's lab in Umea we have identified some of the genes for the cell-type specific molecules including the pan-hemocyte antigen Hemese, a new member of the glycophorin family and L1 lamellocyte marker. A plasmatocyte-antigen, Nimrod was found to be involved phagocytosis. Related genes exist in other insect species and in vertebrates.