title: A new way to detect the danger: Lysosomal cell death induced by a bacterial ribosomal protein.
abstract: The death of immune cells in response to pathogens often dictates the outcome of an infection. In some contexts, pathogens specifically kill immune cells by producing highly potent toxins or by triggering host cell death pathways, thus ensuring successful infections. But for intracellular pathogens and viruses, the death of host cells normally is disastrous for their intracellular life cycle. Our recent experiments with the pathogenLegionella pneumophilarevealed that the bacterial ribosomal protein RpsL is able to trigger lysosomal membrane permeabilization (LMP) and the subsequent macrophage cell death. Interestingly, a lysine to arginine mutation at the 88thresidue, which also confers resistance to the antibiotic streptomycin, substantially impaired the cell death inducing activity of RpsL and allowedL. pneumophilato succeed in intracellular replication, suggesting the convergence of resistance mechanisms to innate immunity and antibiotics. The discovery of lysosomal cell death as an immune response to a bacterial ligand has expanded the spectrum of reactions that host cells can mount against bacterial infection; these observations provide a model to study the pathways that lead to the induction of LMP, a currently poorly understood cellular process involved in the development of many diseases.
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Zhao-Qing
authors.initials: ZQ
authors.lastname: Luo
keywords: Legionella; apoptosis; caspases; cathepsins; innate immunity