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.
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Song, D. et al. Pseudomonas aeruginosa quorum-sensing metabolite induces host immune cell death through cell surface lipid domain dissolution. Nat. Microbiol. https://doi.org/10.1038/s41564-018-0290-8 (2018)
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York, A. Dissolving immune cell membranes. Nat Rev Microbiol 17, 64 (2019). https://doi.org/10.1038/s41579-018-0139-4
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DOI: https://doi.org/10.1038/s41579-018-0139-4