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© The Rockefeller University Press, 0022-1007/2000/2/613/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 4, February 21, 2000 613-624

Original Article

Salmonella-Induced Apoptosis of Infected Macrophages Results in Presentation of a Bacteria-Encoded Antigen after Uptake by Bystander Dendritic Cells

Ulf Yrlida and Mary Jo Wicka

a From the Department of Cell and Molecular Biology, Section for Immunology, Lund University, S-223 62 Lund, Sweden
Department of Cell and Molecular Biology, Section for Immunology, Lund University, Sölvegatan 21, S-223 62 Lund, Sweden.46-46-222-42-1846-46-222-41-67

mary_jo.wick{at}immuno.lu.se

Salmonella 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 not capable of presenting the bacteria-derived antigen despite the fact that they efficiently internalize the apoptotic cells. These data suggest that apoptosis induction by bacterial infection of M{Phi} 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.

Key Words: apoptosis • Salmonella • dendritic cells • macrophages • antigen processing

Abbreviations used in this paper: CCD, cytochalasin D; DC, dendritic cell; LB, Luria broth; M{Phi}, bone marrow–derived macrophage(s); MHC-I and MHC-II, MHC class I and II molecules, respectively; PI, propidium iodide; PP, Peyer's patch.

© 2000 The Rockefeller University Press


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