Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori

Helicobacter pylori persistently colonizes the gastric mucosa of humans, infecting approximately 50% of the population worldwide. The prevalence of H. pylori is decreasing in most parts of the developed world owing to improved sanitation, reduced transmission and the more frequent use of antibiotics in childhood.Initial colonization of the hostile environment of the gastric mucosa by H. pylori requires specific adaptations, including flagellar motility, production of urease, chemotaxis and helical cell shape.To establish persistent infection, H. pylori has evolved to avoid recognition by pattern recognition receptors of the innate immune system and to preferentially activate receptors coupled to anti-inflammatory signalling pathways. The pathogen-associated molecular patterns of this bacterium are substantially less biologically active than those of related Gram-negative enteropathogens.Another H. pylori persistence strategy involves the prevention and manipulation of T cell-mediated adaptive immunity. Specific virulence factors are produced by all strains of H. pylori to block T cell activation, proliferation and effector functions, and to preferentially induce regulatory T cell responses rather than effector T cell responses. Asymptomatic carriers are more likely to preferentially generate TReg responses and harbour denser H. pylori populations than patients with peptic ulcer disease.H. pylori causes gastric disease owing to its production of vacuolating cytotoxin and to a pathogenicity island-encoded type IV secretion system; both virulence determinants act together to promote the production of pro-inflammatory cytokines, to disrupt cell polarity and to cause tissue damage. The advantage of producing these virulence determinants for the bacterium remains poorly understood, but might involve improved iron acquisition or enhanced transmission.As a consequence of the loss of H. pylori from Western societies, the incidence of peptic ulcer disease and gastric cancer has continuously decreased in the affected populations. At the same time, allergies and chronic inflammatory disorders have become more common; epidemiological and experimental evidence suggests an inverse causal association between the loss of H. pylori and the rise in these immunological disorders.