Helicobacter pylori vacuolating cytotoxin inhibits T lymphocyte activation.
Helicobacter pylori (Hp) vacuolating cytotoxin VacA induces cellular vacuolation in epithelial cells. We found that VacA could efficiently block proliferation of T cells by inducing a G1/S cell cycle arrest. It interfered with the T cell receptor/interleukin-2 (IL-2) signaling pathway at the level of the Ca2+-calmodulin-dependent phosphatase calcineurin. Nuclear translocation of nuclear factor of activated T cells (NFAT), a transcription factor acting as a global regulator of immune response genes, was abrogated, resulting in down-regulation of IL-2 transcription. VacA partially mimicked the activity of the immunosuppressive drug FK506 by possibly inducing a local immune suppression, explaining the extraordinary chronicity of Hp infections.
Gebert
Bettina
B
Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, LMU München, Germany.
Fischer
Wolfgang
W
Weiss
Evelyn
E
Hoffmann
Reinhard
R
Haas
Rainer
R
D017209:Apoptosis; D001426:Bacterial Proteins / Q000494:pharmacology / Q000502:physiology*; D001427:Bacterial Toxins / Q000494:pharmacology; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D016213:Cyclins / Q000378:metabolism; D003603:Cytotoxins / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase; D005786:Gene Expression Regulation; D006367:HeLa Cells; D016480:Helicobacter pylori / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D020411:Oligonucleotide Array Sequence Analysis; D016196:S Phase; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology* / Q000502:physiology; D016559:Tacrolimus / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D065095:Calcineurin Inhibitors; D016213:Cyclins; D003603:Cytotoxins; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; C074689:VacA protein, Helicobacter pylori; D019703:Calcineurin; D016559:Tacrolimus