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Multiple Toll-Spätzle Pathways in Drosophila melanogaster Immunity

By Munmun Chowdhury, Chun-Feng Li, Zhen He, Yuzhen Lu, Xusheng Liu, Yufeng Wang, Y Tony Ip, Michael R Strand, Xiao-Qiang Yu

Posted 18 Sep 2018
bioRxiv DOI: 10.1101/420679

The Drosophila melanogaster Toll-Spätzle pathway plays an important role in development and immunity. Drosophila genome encodes nine Toll receptors and six Spätzle (Spz) proteins, and only the canonical Toll-Spz (Toll-1-Spz-1) pathway has been well investigated. In this study, we compared the nine Drosophila Tolls and showed that similarly to Toll, Toll-7 also strongly activated drosomycin promoter. Importantly, we showed that both Toll and Toll-7 interacted with Spz, Spz-2 and Spz-5, and co-expression of Toll or Toll-7 with Spz, Spz-2 and Spz-5 activated the drosomycin promoter. Furthermore, Toll and Toll-7 both recognized vesicular stomatitis virus (VSV) by binding to the VSV glycoprotein. Septic infection in Toll and Toll-7 mutant flies suggested that Toll and Toll-7 differentially affected defense responses in adult males and females after systemic infection by Enterococcus faecalis, Pseudomonas aeruginosa, Candida albicans or VSV. Our results suggest multiple Toll family members activate the expression of antimicrobial peptides. Our results also provide evidence that Toll and Toll-7 bind multiple Spätzle proteins and differentially affect immune defense against different pathogens in adult male and female flies.

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