Harnessing the natural Drosophila-parasitoid model for integrating insect immunity with functional venomics

•Parasitoids induce humoral and cellular immune signaling in Drosophila.•‘Omics’ approaches are integrating insect immunity and functional venomics.•Bioinformatics of predicted venom proteins should direct future experimentation.•Model systems genetics will facilitate testing of parasitoid venom function.

Drosophila species lack most hallmarks of adaptive immunity yet are highly successful against an array of natural microbial pathogens and metazoan enemies. When attacked by figitid parasitoid wasps, fruit flies deploy robust, multi-faceted innate immune responses and overcome many attackers. In turn, parasitoids have evolved immunosuppressive strategies to match, and more frequently to overcome, their hosts. We present methods to examine the evolutionary dynamics underlying anti-parasitoid host defense by teasing apart the specialized immune-modulating venoms of figitid parasitoids and, in turn, possibly delineating the roles of individual venom molecules. This combination of genetic, phylogenomic, and ‘functional venomics’ methods in the Drosophila-parasitoid model should allow entomologists and immunologists to tackle important outstanding questions with implications across disciplines and to pioneer translational applications in agriculture and medicine.