Figure 2
Model of H. pylori factors interacting with host cells. (a) At the apical side of the polarized epithelium H. pylori establishes the first adherence. SabA, BabA, AlpA/B, OipA, HopZ, HorB, etc. are considered as important adhesins that bind to host cell receptors (e.g. Leb, sLex, laminin) and might contribute to NF-кB or MAPK signaling. (b) H. pylori secretes VacA, which forms pores in the host membranes and localizes to mitochondria where it can interfere with apoptosis-related processes. Furthermore, VacA might influence the cellular barrier function by affecting tight junctions; an effect which has also been proposed for soluble urease. Together with H. pylori-secreted HtrA, which directly cleaves the adherence junction molecule E-cadherin, H. pylori efficiently disrupts the epithelial barrier. The T4SS injects the bacterial factor CagA. At the apical side of polarized cells, CagA might translocate via phosphatidylserine and cholesterol. In the cytosol of H. pylori-infected cells, CagA exhibits inhibitory effects on VacA-mediated apoptosis and the integrity of tight and adherence junctions. HtrA-triggered E-cadherin cleavage might be enhanced through H. pylori-induced MMPs and could increase the destabilization of the adherence complex composed of intracellular β-catenin and p120-catenin. Disruption of the E-cadherin complex might contribute to tumor-associated target gene expression in the nucleus and/or to the regulation of the actin cytoskeleton during cell morphological changes and motility. (c) Integrins are expressed at the basolateral side of a polarized epithelium and could be contacted by the T4SS adhesin CagL upon disruption of the intercellular adhesions. CagA translocates across α5β1-integrins and becomes rapidly tyrosine phosphorylated. Phosphorylated CagA then deregulates signal transduction pathways, leading to alterations in gene expression, and strongly interferes with the cytoskeletal rearrangement, which is important for the motogenic response to H. pylori. Peptidoglycan is considered to be another effector that binds Nod1, thereby activating the NF-кB signaling pathways.