Speculations on the activation of ROS generation in C. elegans innate immune signaling

We recently published work demonstrating that ROS (reactive oxygen species) generated by the dual oxidase, Ce-Duox1/BLI-3, in response to infection in Caenorhabditis elegans activates the transcription factor SKN-1, initiating a protective response. Moreover, we showed that the crucial innate immune pathway, p38 MAPK signaling, was responsible for relaying the activating signal. In this commentary, we speculate on the signaling pathway upstream of Ce-Duox1/BLI-3 that triggers its activity. Specifically, we hypothesize that a G-protein signaling pathway comprising Gαq - PLCβ - TPA-1 - DKF-2 activates Ce-Duox1/BLI-3. Our rationale is based on work showing that these components are connected to p38 MAPK signaling and innate immunity in the worm, and investigations in other organisms demonstrating that some of these components are involved in dual oxidase activation.