Review: Pathogenesis of Helicobacter pylori infection.

The original strategies developed by Helicobacter pylori to persistently colonise its host and to deregulate its cellular functions make this bacterium an outstanding model to study host-pathogen interaction and the mechanisms responsible for bacterial-induced carcinogenesis. During the last year, significant results were obtained on the role of bacterial factors essential for gastric colonisation such as spiral shape maintenance, orientation through chemotaxis and the formation of bacteria clonal population islands inside the gastric glands. Particularities of the H pylori cell surface, a structure important for immune escape, were demonstrated. New insights in the bacterial stress response revealed the importance of DNA methylation-mediated regulation. Further findings were reported on H pylori components that mediate natural transformation and mechanisms of bacterial DNA horizontal transfer which maintain a high level of H pylori genetic variability. Within-host evolution was found to be niche-specific and probably associated with physiological differences between the antral and oxyntic gastric mucosa. In addition, with the progress of CryoEM, high-resolution structures of the major virulence factors, VacA and CagT4SS, were obtained. The use of gastric organoid models fostered research revealing, preferential accumulation of bacteria at the site of injury during infection. Several studies further characterised the role of CagA in the oncogenic properties of H pylori, identifying the activation of novel CagA-dependent pathways, leading to the promotion of genetic instabilities, epithelial-to-mesenchymal transition and finally carcinogenesis. Recent studies also highlight that microRNA-mediated regulation and epigenetic modifications, through DNA methylation, are key events in the H pylori-induced tumorigenesis process.

Innate immune activation and modulatory factors of Helicobacter pylori towards phagocytic and nonphagocytic cells.

Helicobacter pylori is an intriguing obligate host-associated human pathogen with a specific host interaction biology, which has been shaped by thousands of years of host-pathogen coevolution. Molecular mechanisms of interaction of H. pylori with the local immune cells in the human system are less well defined than epithelial cell interactions, although various myeloid cells, including neutrophils and other phagocytes, are locally present or attracted to the sites of infection and interact with H. pylori. We have recently addressed the question of novel bacterial innate immune stimuli, including bacterial cell envelope metabolites, that can activate and modulate cell responses via the H. pylori Cag type IV secretion system. This review article gives an overview of what is currently known about the interaction modes and mechanisms of H. pylori with diverse human cell types, with a focus on bacterial metabolites and cells of the myeloid lineage including phagocytic and antigen-presenting cells.