Multiple Toll-Spätzle pathways in Drosophila melanogaster innate immunity

In Drosophila melanogaster, Toll receptor is involved in dorsal-ventral patterning during embryonic development and also in regulation of antimicrobial peptide (AMP) genes in larvae and adult flies. Since the discovery of Drosophila Toll, over ten Toll-like receptors (TLRs) have been identified in vertebrates, which can recognize bacteria, fungi and viruses to trigger different signaling pathways. Drosophila genome encodes nine Toll receptors and six Spätzle (Spz) proteins; however, only Drosophila Toll (Toll-1) and Spz (Spz1) have been well characterized in the canonical Toll pathway. Recently, it has been reported that Drosophila Toll-7 can recognize vesicular stomatitis virus (VSV), Toll-6 and Toll-7 function as neurotrophin receptors. Our preliminary results showed that Drosophila Toll and Toll-7 were functionally active receptors that could activate drosomycin (an AMP gene regulated by the Toll pathway) promoter activity. Our result suggests that both Toll-1 and Toll-7 functions in regulation of AMPs in Drosophila and they may work in concert or respond to different microbial infections. Determination of multiple Toll-Spz pathways will greatly help understanding insect defense mechanisms against microbial infections, and provide insight into the evolution of Toll and TLR signaling pathways from insects to humans.

Keywords: Toll; Toll-like receptor; Spätzle; antimicrobial peptide; neurotrophin.