Quorum-sensing bacteria produce and release molecules that regulate community behaviours. Now, Song et al. report that a quorum-sensing molecule of Pseudomonas aeruginosa induces host immune cell death by causing cell surface lipid domain dissolution. They found that N-(3-oxododecanoyl) homoserine lactone (3OC12 HSL) — an autoinducer of the bacterial LasI–LasR circuitry — incorporates into mammalian plasma membranes and causes lipid domain disruption. This disruption subsequently leads to the spontaneous trimerization of tumour necrosis factor receptor 1 within the membrane, which drives caspase 3–caspase 8-mediated apoptosis. P. aeruginosa released 3OC12 HSL in mouse lung infection experiments, which induced neutrophil apoptosis and supressed host immunity, promoting the survival of P. aeruginosa. Remarkably, a caspase inhibitor diminished the severity of P. aeruginosa infection in mice.