HELICOBACTER PYLORI

Pathogenicity

The pathogenicity of Helicobacter pylori, ie its ability to cause disease, is partly due to bacterial virulence factors and partly to factors related to the host's inflammatory reaction.

The urease activity of Helicobacter pylori is connected - as well as with the nesting and energy production capacity - with the pathogenicity of the microorganism itself. This substance, together with the membrane lipopolysaccharide (LPS), with various cytotoxic factors and toxins (VacA and CagA), induces an inflammatory response at the gastric level, which in turn underlies the diseases caused by Helicobacter pylori (such as gastritis antral and peptic ulcer). Although they are commissioned to eradicate the infection, the mediators of inflammation produced by our organism can in fact exert a pathological effect on the gastric mucosa. In many cases, however, this local inflammation is not sufficient to eradicate Helicobacter pylori, given the ability of the bacterium to produce superoxide dismutase and catalase to protect itself from neutrophil phagocytosis. Lewis present on the cells of the gastric mucosa - the inflammatory response of the host is often contained and if on the one hand all this favors the survival of the bacterium, on the other it explains why in most people there is no development of symptomatic pathologies.

The condition of chronic gastric hyperacidity associated with Helicobacter pylori infection can lead to the development of so-called duodenal and esophageal metaplasias, due to the slow process of adaptation of the tissues to the excessive acidity of the chyme that reaches the small intestine or goes back into the esophagus during episodes of reflux. The inflammatory response caused by the infection in fact stimulates the G cells of the stomach to secrete more gastrin, a hormone which in turn acts on the region of the gastric body by stimulating the secretion of hydrochloric acid.

Helicobacter pylori gastritis is also a risk factor for gastric cancer, along with environmental, dietary and genetic influences. The correlation between Helicobacter pylori infection and cancer is especially valid for some cancers, such as adenocarcinoma and MALT-associated Primary Gastric Lymphoma. pylori in 100, while 10 to 20 individuals will develop gastric and duodenal ulcers.

The possibility of leading to tumor formation is favored by a region of the Helicobacter pylori genome called cag-PaI. The strains carrying the genes that code for this region (CagA positive) are more virulent, they reach a higher bacterial density in the mucosa gastric and cause more inflammation than CagA negative strains.Fundamental for the virulence of the bacterium is in fact the presence of the Cag-PAI pathogenicity island, containing about thirty genes which, among other things, encode for a type IV secretion system that allows direct injection into the gastric epithelial cells of a series of cytotoxic products, including VacA and CagA, regulated by other genes of the island. This Cag-PaI region is found on average in 50-70% of bacterial strains isolated in industrialized countries, which are therefore more virulent than the others.

VacA is a vacuolizing toxin which causes the fusion of endosomes and lysosomes at the level of the gastric epithelial cells. CagA, on the other hand, is a protein that stimulates the secretion of IL-8 by the cells of the gastric mucosa; Interleukin 8 is an important chemotactic factor capable of conveying granulocytes, lymphocytes and monocytes, and as such plays a leading role in the induction of the inflammatory process.

The non-specific and specific immune response to Helicobacter pylori infection can also assume a systemic character, through the release of cytokines such as interleukin 6 (IL-6) and Tumor Necrosis Factor α (TNFα). This assumption, together with epidemiological studies, has led the researchers to investigate the possible role of the bacterium in the development of pathologies unrelated to the alimentary canal; in this regard there is evidence of possible correlations between Helicobacter pylori and ischemic heart disease, cerebral vasculopathy, primary Raynaud's disease, idiopathic migraine, autoimmune diseases, injuries skin and idiopathic iron deficiency anemia.