Sensing Cytosolic RpsL by Macrophages Induces Lysosomal Cell Death and Termination of Bacterial Infection

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The death of the host cell during infection can be triggered by one or more microbial molecules; this “live or die” selection provides effective means for the dissection of immune recognition mechanisms as well as for the identification of the microbial molecules responsible for such responses. We found that infection of primary mouse macrophages by Legionella pneumophila strains harboring wild type RpsL, the S12 component of the bacterial ribosome, causes macrophage death by a mechanism independent of the three inflammatory caspases, caspase 1, 7 and 11. Importantly, although both confer resistance to streptomycin at indistinguishable effectiveness, the K88R, but not the K43N mutation in RpsL enables L. pneumophila to replicate in macrophages. Purified RpsL and RpsLK43N physically delivered into macrophages cause cell death by inducing damage to lysosomal membranes and the release of cathepsins. We also found that the lysosomal protease cathepsin B is required for efficient RpsL-induced cell death but its absence is not sufficient for macrophages to support intracellular bacterial replication. Thus, RpsL functions as an immune induction molecule to trigger one or more signaling cascades that leads to lysosomal cell death as well as the termination of bacterial replication.

Vyšlo v časopise: Sensing Cytosolic RpsL by Macrophages Induces Lysosomal Cell Death and Termination of Bacterial Infection. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004704
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004704

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