Insights into insect innate immunity. J.R. Delaney , K.V. Anderson. Developmental Genetics, Sloan-Kettering Institute, New York, NY.

   All organisms need to protect themselves from pathogenic and parasitic attack. Even unicellular organisms produce antibiotic compounds that kill other microbes. In higher organisms, such as Drosophila and Homo sapiens, multiple humoral and cellular immune defense mechanisms have developed. Both flies and vertebrates produce anti-microbial peptides. In flies, central production of these compounds takes place in the fat body. Drosophila macrophages, like vertebrate macrophages, engulf pathogens and produce soluble factors in response to infection. Lamellocytes encapsulate pathogens. Crystal cells produce components of melanin synthesis. Molecular data indicate that the signal pathways that control Drosophila and vertebrate immune responses are conserved. However, large gaps still exist in our understanding of these processes. Analysis of the genetically amenable Drosophila will allow the identification of aspects of innate immunity that remain hidden in mammalian experimental systems. We have conducted an EMS-mutagenesis screen of the Drosophila X-chromosome to identify novel components of the immune response. We scored 1400 viable lines. 8 lines failed to express a lacZ reporter gene under the control of the promoter region from the gene encoding the anti-microbial peptide diptericin in response to infection. 23 lines have been identified based on their inability to suppress bacterial growth. 13 lines failed to melanize at a wound site and another 12 lines spontaneously generated melanin deposits; these phenotypes may be indicative of crystal cell defects. One mutant line of interest failed to express several endogenous anti-microbial peptides in response to infection. Homozygous females from this line produce embryos with patterning defects. Endogenous immune responses and blood cell composition will be examined in all mutant lines. Those mutations that have a broad impact on immune responses may define early pathogen recognition, activation or signaling events.