Salmonella-induced apoptosis of infected macrophages results in presentation of a bacteria-encoded antigen after uptake by bystander dendritic cells

Salmonella il,typhimurium is a gram-negative bacterium that survives and replicates inside vacuolar compartments of macrophages. Infection of macrophages with S. typhimurium grown under conditions allowing expression of the type III secretion system results in apoptotic death of the infected cells. Here, we show that infection of bone marrow-derived macrophages (M Phi) with wild-type S. typhimurium 14028 results in presentation of epitopes derived from a bacteria-encoded antigen on major histocompatibility complex (MHC) class I and MHC class II molecules after internalization of apoptotic M Phi by bystander dendritic cells (DCs). In contrast, infection of M Phi with the phoP constitutive mutant strain CS022, which does not induce apoptosis in infected M Phi, does not result in presentation of a bacteria-derived antigen by bystander DCs unless the infected M Phi are induced to undergo apoptosis by treatment with lipopolysaccharide and ATP. DCs appear to be unique in their ability to present antigens derived from M Phi induced to undergo apoptosis by Salmonella, as bystander M Phi, are no;capable of presenting the bacteria-derived antigen despite the fact that riley efficiently internalize the apoptotic cells. These data suggest that apoptosis induction by bacterial infection of MCD may not be a quiescent death that allows the bacteria to escape recognition by the immune system, but rather may contribute to an antimicrobial immune response upon engulfment by bystander DCs.