Bacterial blockade of host protein synthesis triggers cell death in dendritic cells to restrict Legionella pneumophilainfection

Abstract

Abstract Legionella pneumophila is a facultative intracellular bacterial pathogen that is responsible for a pneumonia called Legionnaire’s disease. Legionella invades cells by using a type IV secretion system that delivers effector proteins into the host cell cytosol to facilitate its intracellular survival and replication. Macrophages serve as the primary replicative niche for Legionella. In contrast, dendritic cells (DCs) have been shown to rapidly restrict Legionella infection by activating cell death. The host and bacterial factors that induce this response remain elusive. We found that DCs undergo caspase-dependent cell death and that this response is triggered by a subset of secreted effectors that block host protein synthesis. Specifically, we show that these effectors decrease the levels of pro-survival proteins in DCs, thus leaving cells poised to undergo cell death. Altogether, our data show that pro-survival molecules in DCs serve as guard proteins that detect pathogenic activities to limit bacterial replication. Supported by a National Science Foundation Graduate Research Fellowship Program (DGE-2236662)