Toll-mediated airway homeostasis is essential for fly survival upon injection of RasV12-GFP oncogenic cells

Toll signaling is well known for its pivotal role in the host response against the invasion of external pathogens. Here, we investigate the potential involvement of Toll signaling in the intersection between the host and oncogenic cells. We show that loss of myeloid differentiation factor 88 (Myd88) leads to drastic fly death after the injection of RasV12-GFP oncogenic cells. Transcriptomic analyses show that challenging flies with oncogenic cells or bacteria leads to distinct inductions of Myd88-dependent genes. We note that downregulation of Myd88 in the tracheal system accounts for fly mortality, and ectopic tracheal complementation of Myd88 rescues the survival defect in Myd88 loss-of-function mutants following RasV12-GFP injection. Further, molecular and genetic evidence indicate that Toll signaling modulates fly resistance to RasV12-GFP cells through mediating airway function in a rolled-dependent manner. Collectively, our data indicate a critical role of Toll signaling in tracheal homeostasis and host survival after the injection of oncogenic cells. [Display omitted] •Toll signaling plays a critical role in fly survival after injection of oncogenic cells•Toll signaling does not modulate the proliferation of injected oncogenic cells•Downregulation of Toll signaling leads to defects in tracheal branch and fly breath•Toll signaling mediates the tracheal integrity in a rolled-dependent manner Ji et al. report that the canonical Toll signaling pathway is essential for fly survival after injection of RasV12-GFP oncogenic cells. It modulates tracheal integrity and fly oxygen consumption through targeting rolled.