RESUMO
H. pylori has developed a unique set of virulence factors, which allow its survival in a unique ecological niche, the human stomach. The vacuolating cytotoxin (VacA) and the cytotoxin-associated antigen (CagA) are major bacterial factors involved in modulating the host. VacA, so far mainly regarded as a cytotoxin for the gastric epithelial cell layer, apparently has profound effects in modulating the immune response. In this review we discuss some of the classical effects of VacA, such as cell vacuolation, and compare them with more recently identified mechanisms of VacA on immune cells.
Assuntos
Proteínas de Bactérias/imunologia , Mucosa Gástrica/microbiologia , Gastrite/microbiologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Antígenos de Bactérias/imunologia , Apoptose/imunologia , Aderência Bacteriana/imunologia , Mucosa Gástrica/citologia , Mucosa Gástrica/imunologia , Gastrite/imunologia , Humanos , Ativação Linfocitária/imunologia , Linfócitos T/imunologia , Linfócitos T/microbiologia , Vacúolos/imunologiaRESUMO
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.
