Innate Immunity

The cell mediated immunity of Drosophila

We are interested in understanding fundamental processes in innate immunity. We focus on the mechanisms governing the development and effector functions of the Drosophila innate immune system, but we use human cells and other organisms too, when it is applicable.  Like humans, the Drosophila has a sophisticated immune defense with humoral and cellular elements, and homologs with human genes are also implicated. The detailed molecular mechanisms of the humoral response are now well understood. In contrast, much less is known about the cellular part of the immune response in Drosophila, which involves recognition, activation, mobilization, proliferation, killing of parasites, and phagocytosis. Our laboratory is using a wide range of technology, including genetic screens, tools of immunology, molecular biology, molecular genetics, functional genomics, mass spectrometry, immuno-electron microscopy and live imaging to reveal novel key factors involved in recognition and elimination of foreign substances, as microbes and parasitoids.

The defense against parasites is under strong evolutionary pressure and we believe that a comparative study of immunity is informative about the basic principles involved. For such studies, we exploit the wealth of data of Drosophilidae, including the genomes of several Drosophila species. We further investigate the regulation of the plasticity and independence of hemocyte lineages (Fig.1) as demonstrated by the conversion of phagocytic plasmatocytes to non-phagocytic cells capable of encapsulating parasitic wasp eggs.

Fig. 1 Plasticity and trans-differentiation of Drosophila hemocytes. Márkus et al., J Innate Immunity, DOI: 10.1159/000369618

We have identified a novel cell type, named the Multinucleated Giant Hemocyte (MGH) in several species of the ananassae subgroup of Drosophilidae (Fig.2) and in the invasive species, Zaprionus indianus. These species have a unique, highly effective defense mechanism with the involvement of MGHs to neutralize parasites. We are analyzing the defense strategies used by these species and the role of two-step genome amplification in the development of MGHs and in the effective immune response. We have generated immunological markers for all cell types in D. ananassae, D. bipectinata and Z. indianus to follow the track of the differentiation lineages. On the basis of homologies in the regulatory regions, we have generated transgenic lines in D. ananassae and we are building a genetic system to use them in combination with the immunological markers, as we did in D. melanogaster.  In these studies we are also using the transcriptome databases generated by us in D. ananassae and Z. indianus and carry out a comparative analysis using the databases of D. melanogaster and other species, when it is applicable.

Fig.2 Encapsulation of the parasitoid larva by D. ananassae MGHs (Róbert Márkus)

Interactions of insect hosts with opportunistic pathogens

Our laboratory is studying the interaction between Drosophila and opportunistic pathogen fungi to reveal the virulence factors and the defense against infection. Here we use a collection of mutant Drosophila stocks and genome-edited fungi using septic injury assay and phagocytosis (Fig. 3). We believe that the fundamental knowledge generated by studying this type of interaction will have general biological relevance.

We also have an interest in the functional heterogeneity of the cellular elements of the honey bee (Apis mellifera) immune system and in the molecular mechanisms involved in the recognition of entomopathogenic microbes. So far we identified cell-type specific molecules for hemocyte subpopulations which could be used as reference markers for functional hemocyte subsets.

Fig. 3. Septic injury assay and phagocytosis of opportunistic fungi