Infection with Listeria monocytogenes impairs sialic acid addition to host cell glycoproteins.
Listeria monocytogenes is a facultative intracellular bacterium that causes severe disease in neonates and immunocompromised adults. Although entry, multiplication, and locomotion of Listeria in the cytosol of infected cells are well described, the impact of such infection on the host cell is unknown. In this report, we investigate the effect of L. monocytogenes infection on MHC class I synthesis, processing, and intracellular trafficking. We show that L. monocytogenes infection interferes with normal processing of N-linked oligosaccharides on the major histocompatibility complex (MHC) class I heavy chain molecule, H-2Kd, resulting in a reduced sialic acid content. The glycosylation defect is more pronounced as the infection progresses and results from interference with the addition of sialic acid rather than its removal by a neuraminidase. The effect is found in two different cell lines and is not limited to MHC class I molecules since CD45, a surface glycoprotein, and LGP120, a lysosomal glycoprotein, are similarly affected by L. monocytogenes infection. The glycosylation defect is specific for infection by L. monocytogenes since neither Trypanosoma cruzi nor Yersinia enterocolitica, two other intracellular pathogens, reproduces the effect. The resultant hyposialylation of H-2Kd does not impair its surface expression in infected cells. Diminished sialic acid content of surface glycoproteins may enhance host-defense by increasing susceptibility to lysis and promoting clearance of Listeria-infected cells.
Department of Internal Medicine, Yale University Medical School, New Haven, Connecticut 06520-8022.
M S
MS
Villanueva
C J
CJ
Beckers
E G
EG
Pamer
D000818:Animals; D020126:Brefeldin A; D002460:Cell Line; D003517:Cyclopentanes / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D006023:Glycoproteins / Q000096:biosynthesis* / Q000302:isolation & purification; D006026:Glycoside Hydrolases / Q000378:metabolism; D006031:Glycosylation; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000472:pathogenicity* / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012794:Sialic Acids / Q000378:metabolism*
D003517:Cyclopentanes; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011500:Protein Synthesis Inhibitors; D012794:Sialic Acids; D020126:Brefeldin A; D007371:Interferon-gamma; D006026:Glycoside Hydrolases; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid