Interaction of Helicobacter pylori with professional phagocytes: role of the cag pathogenicity island and translocation, phosphorylation and processing of CagA.
Chronic infection of the human gastric mucosa with Helicobacter pylori is a major cause of gastroduodenal pathologies, including peptic ulcerations, mucosa-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Helicobacter pylori strains carrying the cag pathogenicity island, which encodes an active type IV protein secretion system (cag+ or type I strains), are preferentially associated with strong gastric inflammation and severe disease. We show here that cag+ H. pylori strains use the type IV secretion system to inject the bacterial protein CagA into various types of professional phagocytes, including human polymorphonuclear leucocytes (PMNs) and the human and murine macrophage cell lines THP-1 and J774A.1 CagA is rapidly tyrosine phosphorylated and proteolytically processed to generate a stable 35-45 kDa C-terminally tyrosine-phosphorylated protein fragment. H. pylori was efficiently ingested by the different types of phagocytic cells. A chromosomal deletion of the complete pathogenicity island had no significant effect on the rate of ingestion. Furthermore, the survival rate of H. pylori in the phagosome was unchanged between the wild type and a deletion mutant lacking the type IV secretion system. Thus, the type IV secretion system seems to be involved neither in active phagocytosis resistance nor in prolonged survival of the bacteria in phagocytic cells.
Odenbreit
S
S
Max von Pettenkofer Institut für Hygiene und Medizinische Mikrobiologie, München, Germany.
Gebert
B
B
Püls
J
J
Fischer
W
W
Haas
R
R
D000818:Animals; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016480:Helicobacter pylori / Q000737:chemistry / Q000472:pathogenicity*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry; D010586:Phagocytes / Q000276:immunology / Q000382:microbiology*; D010587:Phagocytosis; D010766:Phosphorylation; D014162:Transfection; D014170:Transformation, Genetic; D014443:Tyrosine / Q000378:metabolism
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D010446:Peptide Fragments; C080866:cagA protein, Helicobacter pylori; D014443:Tyrosine