Listeria monocytogenes infects human endothelial cells by two distinct mechanisms.
Infection of endothelial cells by bacteria may be an important component of the bacteria's ability to escape host defenses and cause disease. Listeria monocytogenes cause sepsis and central nervous system infection in domesticated animals and immunocompromised humans, suggesting that this bacterium interacts with endothelial cells in a significant fashion. The experiments presented here tested the hypothesis that L. monocytogenes can invade and replicate within human endothelial cells. We found that L. monocytogenes grows readily in umbilical vein endothelial cells and that its intracellular life cycle involves phagosomal escape, F-actin-based motility, and cell-to-cell spread. We found that L. monocytogenes invaded endothelial cells by cell-to-cell spread from adherent mononuclear phagocytes which were previously infected by this bacterium. Interestingly, L. monocytogenes mutants lacking the invasion protein, internalin, bound less well to endothelial cells than did wild-type bacteria in the absence, but not the presence, of serum, and their invasion of endothelial cells was diminished under both conditions. Thus, endothelial cell infection by L. monocytogenes can occur by two distinct mechanisms: direct bacterial invasion of the endothelial cells in an internalin-mediated fashion or cell-to-cell spread from adherent, infected mononuclear phagocytes. These data support the idea that endothelial cell infection by L. monocytogenes is an important event in the pathogenesis of listeriosis.
Drevets
D A
DA
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
Sawyer
R T
RT
Potter
T A
TA
Campbell
P A
PA
D000199:Actins / Q000378:metabolism; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D004730:Endothelium, Vascular / Q000382:microbiology*; D006801:Humans; D008089:Listeria monocytogenes / Q000254:growth & development / Q000472:pathogenicity*; D008088:Listeriosis / Q000209:etiology*; D008969:Molecular Sequence Data; D010586:Phagocytes / Q000382:microbiology
D000199:Actins; D001426:Bacterial Proteins; D017931:DNA Primers; C069761:internalin protein, Bacteria