The Immunomodulator VacA Promotes Immune Tolerance and Persistent Helicobacter pylori Infection through Its Activities on T-Cells and Antigen-Presenting Cells.
VacA is a pore-forming toxin that has long been known to induce vacuolization in gastric epithelial cells and to be linked to gastric disorders caused by H. pylori infection. Its role as a major colonization and persistence determinant of H. pylori is less well-understood. The purpose of this review is to discuss the various target cell types of VacA and its mechanism of action; specifically, we focus on the evidence showing that VacA targets myeloid cells and T-cells to directly and indirectly prevent H. pylori-specific T-cell responses and immune control of the infection. In particular, the ability of VacA-proficient H. pylori to skew T-cell responses towards regulatory T-cells and the effects of Tregs on H. pylori chronicity are highlighted. The by-stander effects of VacA-driven immunomodulation on extragastric diseases are discussed as well.
Institute of Molecular Cancer Research, University of Z&#252;rich, Winterthurerstr. 190, 8057 Z&#252;rich, Switzerland.
Aleksandra
A
Djekic
Institute of Molecular Cancer Research, University of Z&#252;rich, Winterthurerstr. 190, 8057 Z&#252;rich, Switzerland. mueller@imcr.uzh.ch.
Anne
A
Müller
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001426:Bacterial Proteins / Q000378:metabolism*; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology; D016480:Helicobacter pylori / Q000378:metabolism* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D037521:Virulence Factors
D001426:Bacterial Proteins; C074689:VacA protein, Helicobacter pylori; D037521:Virulence Factors
T-cell priming; effector T-cells; immune tolerance; myeloid cells; persistent infection; professional antigen-presenting cells; regulatory T-cells