Explosive cytotoxicity of ‘ruptoblasts’ bridges hormonal surveillance and immune defense

Cytotoxic killing is an essential immune function, yet its cellular mechanisms have been characterized in only a few model species. Here, we show that planarian flatworms harness a unique cytotoxic strategy. In planarians, activin, a hormone regulating regeneration and reproduction, also acts as an inflammatory cytokine. Overactivation of activin signaling – through protein injection, genetic chimerism, or bacterial infection – triggers ‘ruptoblasts’, an undocumented immune cell type, to undergo ‘ruptosis’, a unique mode of cell bursting that eliminates nearby cells and bacteria in mere minutes, representing one of the fastest cytotoxic mechanisms observed. Ablating ruptoblasts suppresses inflammation but compromises bacterial clearance, highlighting ruptoblasts’ broad-spectrum immune functions. We further identified ruptoblast-like cells in diverse basal bilaterians, unveiling an alternative strategy that couples hormonal regulation with immune defense and expanding the landscape of evolutionary immune innovations.