Functional role of thioester-containing proteins in the Drosophila anti-pathogen immune response

Thioester-containing proteins (TEPs) are present in many animal species ranging from deuterostomes to protostomes, which emphasizes their evolutionary conservation and importance in animal physiology. Phylogenetically, insect TEPs share sequence similarity with mammalian α2-macroglobulin. Drosophila melanogaster is specifically considered a superb model for teasing apart innate immune processes. Here we review recent discoveries on the involvement of Drosophila TEPs in the immune response against bacterial pathogens, nematode parasites, and parasitoid wasps. This information generates novel insights into the role of TEPs as regulators of homeostasis in Drosophila and supports the complexity of immune recognition and specificity in insects and more generally in invertebrates. These developments together with recent advances in gene editing and multi-omics will enable the fly immunity community to appreciate the molecular and mechanistic contributions of TEPs to the modulation of the host defense against infectious disease and possibly to translate this information into tangible therapeutic benefits.