Immune suppression by parasitoid wasps of Drosophila: Studies on virus-like particles, virulence, and genome-wide expression analysis

D. melanogaster has a primitive but powerful innate immune system consisting of humoral and cellular components. Cellular immune responses are mediated by plasmatocytes that carry out phagocytosis, crystal cells that mediate melanization, and lamellocytes which encapsulate large parasites. Encapsulation is the major defense of Drosophila larvae against eggs of parasitoid wasps. Parasitoid wasps, however, have evolved to either actively suppress, or passively avoid encapsulation. For instance, infection by the wasps Leptopilina heterotoma or L. victoriae, eliminates activated plasmatocytes and lamellocytes via apoptosis and lysis respectively. Virus-like particles (VLPs) produced by L. heterotoma mediate the lysis of lamellocytes and consequently suppress encapsulation. Avirulent strains of wasps, such as L. boulardi-G486 , are less successful at parasitizing Drosophila, and their VLPs do not cause lamellocyte lysis. Our main goals are (1) To understand the nature of humoral and cellular immune responses of D. melanogaster infected by parasitoid wasps differing in the degree and mechanisms of virulence. (2) To understand virulence mechanisms adapted by these wasps, the structure of their VLPs, and to determine how virulence factors disrupt host defense responses. We describe the biogenesis and fine structure of previously undescribed VLPs found in L. victoriae. In vitro, these VLPs induce the lysis of lamellocytes but with slower kinetics than L. heterotoma VLPs. Purified VLPs from these two wasp species contain at least 4 major proteins. The most abundant proteins, p40 in L. heterotoma and p47.5 in L. victoriae, cross react with polyclonal antisera raised against L. heterotoma VLPs. Immuno-EM staining localizes these proteins to VLP surfaces. Significantly, anti-p40 antibodies block lamellocyte lysis induced by either L. heterotoma or L. victoriae VLPs. A comparison of changes in global gene expression patterns of D. melanogaster larvae in response to L. heterotoma versus L. boulardi infection reveals significant differences, both in the number and nature of genes. These differences in gene expression patterns will provide clues into the molecular mechanisms of virulence and immune suppression used by parasitoid wasps.