<i>Drosophila melanogaster</i> Toll-9 elicits antiviral immunity against Drosophila C virus

Insects rely on innate immunity and RNA interference (RNAi) to combat viral infections. Our study underscores the pivotal role of <i>Drosophila</i> Toll-9 in antiviral immunity, aligning with findings in <i>Bombyx mori</i>, where Toll-9 activation upregulates the RNAi component <i>Dicer2</i>. We demonstrate that <i>Drosophila</i> Toll-9 functions as a pattern recognition receptor (PRR) for double-stranded RNA (dsRNA) during Drosophila C virus (DCV) infection, akin to mammalian Toll-like receptors (TLRs). Toll-9 activation during DCV infection leads to the upregulation of <i>Dicer2</i> and <i>Argonaute2</i> and dephosphorylation of AKT. This study also reveals that Toll-9 localizes in endosomal compartments where it interacts with dsRNA. These insights enhance our understanding of <i>Drosophila</i> innate immune mechanisms, reflecting the evolutionary conservation of immune responses across diverse species and providing impetus for further research into the conserved roles of TLRs across the animal kingdom.