The Immunomodulator VacA Promotes Immune Tolerance and Persistent Helicobacter pylori Infection through Its Activities on T-Cells and Antigen-Presenting Cells

• Main Authors: Aleksandra Djekic, Anne Müller
• Format: Article
• Language: English
• Published: MDPI AG 2016-06-01
• Series: Toxins
• Subjects: persistent infection; myeloid cells; professional antigen-presenting cells; T-cell priming; effector T-cells; regulatory T-cells; immune tolerance
• Online Access: http://www.mdpi.com/2072-6651/8/6/187

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.