Natterin an aerolysin-like fish toxin drives IL-1?-dependent neutrophilic inflammation mediated by caspase-1 and caspase-11 activated by the inflammasome sensor NLRP6

Natterin is an aerolysin-like pore-forming toxin responsible for the toxic effects of venom medically significant fish Thalassophryne nattereri. Using a combination pharmacologic and genetic loss-of-function approaches we conduct systematic investigation regulatory mechanisms that control Natterin-induced neutrophilic inflammation in peritonitis model. Our data confirmed capacity to induce strong sustained leading systemic inflammatory lung infiltration revealed overlapping paths its control. We found induced extracellular release mature IL-1? production IL-33 by bronchial epithelial cells. dependence both ST2/IL-33 IL-17A/IL-17RA signaling on local neutrophils migration, as well crucial role IL-1?, caspase-1 caspase-11 inflammation. The triggered was gasdermin-D-dependent inflammasome process, despite cells did not die pyroptosis. Finally, mediated non-canonical NLRP6 NLRC4 adaptors through ASC interaction, independent NLRP3. highlight process dependent activation can be target pharmacological intervention accidents T. nattereri, which does have adequate specific therapy.