Seminar

The Host Defense of Insects: A Paradigm for Innate Immunity

Prof. Jean Marc Reichhart

Professor Jean-Marc Reichhart's group has been working since 1985 on the innate immune system. The adaptative immune system with its antibodies, B and T cells arose only once during evolution, around 500 million years ago probably in the first vertebrates. This specific immune system acts in concert with the innate immune system in roughly 45000 vertebrate species as a defence against invading microorganisms. In all invertebrates, the defence mechanisms are purely innate. In Drosophila, an infection provokes the rapid synthesis of powerful antibiotic peptides by the fat body. As an example, the basal level of expression of the antifungal peptide DROSOMYCIN, is increased a thousand fold within 30 minutes of septic injury in larvae or adults. The control of this expression involves at least two pathways that, for sake of simplicity, Professor Reichhart refers to as the TOLL and the IMD pathways. The paramount role of the TOLL and IMD pathways in the host defence of Drosophila is illustrated by experiments in which mutant flies are challenged with fungi or bacteria. In TOLL-deficient mutants, survival to fungal, but not to bacterial infection, is severely compromised. By contrast, IMD mutants are markedly affected by bacterial infections but resist fungi with a survival pattern similar to that of wild-type flies. In Vertebrates, recognition of microbes by the innate immune system takes place at the cellular level by a family of transmembrane receptors homolog to Drosophila Toll, namely the Toll like receptors (TLRs). In Drosophila however, these recognition events take place in the open circulatory system via soluble excreted recognition proteins like the peptidoglycan recognition proteins (PGRPs) and the glucan binding proteins (GNBPs). In turn, these recognition steps must be conveyed onto Toll by extracellular proteolytic signalling pathways. Upstream of the IMD pathway, other PGRPs are recognizing Gram-negative microbial determinants. Professor Jean-Marc Reichhart's group is now interested in how these two pathways are activated and regulated.