The mechanism of cell death in Listeria monocytogenes-infected murine macrophages is distinct from apoptosis.
Various pathogenic bacteria with the capacity to live within eukaryotic cells activate an apoptotic program in infected host cells. Induction of apoptosis by Listeria monocytogenes in murine dendritic cells and hepatocytes has been described. Here we address the questions of whether and how the pathogen kills macrophages, its most important habitat. Employing several complementary techniques aimed at discriminating between apoptosis and necrosis, we show that murine bone marrow-derived macrophages (BMM) undergo delayed necrosis but not apoptosis when infected with listeriolysin (Hly)-producing L. monocytogenes. This pathogen failed to elicit apoptotic morphology, DNA fragmentation, and surface annexin V binding of macrophages, in contrast to Shigella flexneri infection or gliotoxin treatment, which were used as positive controls. Furthermore, macrophages infected with L. monocytogenes released lower quantities of interleukin-1beta (IL-1beta) than did Shigella flexneri-infected ones, indicating diminished or even absent activation of IL-1-converting enzyme in macrophages harboring L. monocytogenes. We conclude that murine BMM die by necrosis after several hours of cytoplasmic replication of L. monocytogenes. The pathogen may benefit from this feature by the possibility of taking advantage of cells of "pseudo-healthy" appearance, thus avoiding rapid elimination by other phagocytes.
Barsig
J
J
Department of Immunology, University of Ulm, Germany.
Kaufmann
S H
SH
D000818:Animals; D017209:Apoptosis; D001427:Bacterial Toxins; D016923:Cell Death; D002462:Cell Membrane / Q000737:chemistry; D002467:Cell Nucleus / Q000473:pathology; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006460:Hemolysin Proteins; D007375:Interleukin-1 / Q000096:biosynthesis; D008089:Listeria monocytogenes / Q000276:immunology / Q000472:pathogenicity*; D008264:Macrophages / Q000382:microbiology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D010718:Phosphatidylserines / Q000032:analysis; D012763:Shigella flexneri / Q000276:immunology / Q000472:pathogenicity; D013045:Species Specificity
D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D007375:Interleukin-1; D010718:Phosphatidylserines; C038705:hlyA protein, Listeria monocytogenes