Mechanism of Legionella rpsL-induced lysosomal cell death in macrophages

Determine the molecular mechanism underlying the infection-induced lysosomal cell death observed in mouse bone marrow-derived macrophages following infection with Legionella pneumophila strains harboring wild-type rpsL (e.g., Lp02 rpsLwt), and ascertain the upstream cellular events that lead to lysosomal membrane permeabilization during this process.

Background

Infections by Legionella pneumophila strains carrying wild-type rpsL, such as Lp02 rpsLwt, have been reported to induce extensive lysosomal damage and apoptosis in mouse bone marrow-derived macrophages, terminating bacterial replication. While lysosomes are implicated in this response, the precise molecular mechanism driving this unique infection-induced cell death has not been defined.

Clarifying the upstream signaling and cellular events that culminate in lysosomal membrane permeabilization would fill a critical gap in understanding how immunogenic cell death is triggered by specific pathogen-associated factors, potentially revealing new therapeutic targets to control intracellular bacterial infections.