Expression of Helicobacter pylori Virulence Factors and Associated Expression Profiles of Inflammatory Genes in the Human Gastric Mucosa

Abstract

Helicobacter pylori virulence factors have been suggested to be important in determining the outcome of infection. The H. pylori adhesion protein BabA2 is thought to play a crucial role in bacterial colonization and in induction of severe gastric inflammation, particularly in combination with expression of CagA and VacA. However, the influence of these virulence factors on the pathogenesis of H. pylori infection is still poorly understood. To address this question, the inflammatory gene expression profiles for two groups of patients infected with triple-negative strains (lacking expression of cagA, babA2, and vacAs1 but expressing vacAs2) and triple-positive strains (expressing cagA, vacAs1, and babA2 but lacking expression of vacAs2) were investigated. The gene expression patterns in the antrum gastric mucosa from patients infected with different H. pylori strains were very similar, and no differentially expressed genes could be identified by pairwise comparisons. Our data thus suggest that there is a lack of correlation between the host inflammatory responses in the gastric mucosa and expression of the babA2, cagA, and vacAs1 genes.Helicobacter pylori infection is widespread in humans; it is present in 20 to 50% of the population in developed countries and 80% of the population in developing countries (43). Most infected individuals display only asymptomatic gastritis, whereas a small proportion develop severe disease, including peptic ulceration and gastric malignancy. Although the factors that determine the outcome of the infection are not well understood, bacterial virulence factors have been suggested to play important roles.One of the major virulence factors of H. pylori is the vacuolating cytotoxin (VacA), which causes cytoplasmic vacuolization in gastric epithelial cells (41). Another well-characterized virulence factor is the cytotoxin-associated antigen (CagA), which is encoded by one of the genes located in the cag pathogenicity island (PAI) (8). Strains expressing vacAs1 and/or cagA are present at a higher frequency in patients with duodenal ulcers, atrophic gastritis, and gastric carcinoma (2,5,13,17,23) and are referred to as type I strains. In contrast, type II strains, which lack the cagA gene, present a nontoxic form of VacA and are considered less virulent (37, 46). The blood group antigen binding adhesin (BabA), encoded by the babA2 gene, has previously been shown to mediate adherence of H. pylori to the Lewis b blood group antigen on human gastric epithelial cells (6,7,19). The attachment may facilitate H. pylori colonization and efficient delivery of virulence factors such as VacA or CagA to the host cells, resulting in severe gastric inflammation. It has indeed been shown that strains with babA2, particularly when it is present together with cagA and vacAs1 (referred to as triple-positive strains here), are more often associated with duodenal ulcers and adenocarcinoma than the strains without babA2 (15). Moreover, triplepositive strains are detected more frequently in patients with severe ...

Relevance of IL-1 and TNF gene polymorphisms on interleukin-1β and tumor necrosis factor-α gastric mucosal production

“…Concerning cytokine levels, no association between corpus and antrum mucosal concentrations of IL-1␤ and TNF-␣ with respect to CagA/ VacA status was observed. These findings are consistent with a number of previous studies that reported similar gene expression patterns in the gastric mucosa of patients infected with different H. pylori strains, suggesting that the expression levels of some cytokines, including IL-1␤ and TNF-␣, are independent of the presence of cagA or vacA genes [44,55,56]. On the other hand, the prevalence of infection with H. pylori or cagA/vacA strains resulted in no differences among carriers of the IL1 and TNF gene polymorphisms analyzed in this study.…”

Association of iceA and babA genotypes in Helicobacter pylori strains with patient and strain characteristics

“…and babA2?) and duodenal ulcers have been found in Portugal, Germany, Finland and Cuba, however, no such association have been observed in Sweden (Olfat et al 2005;Wen et al 2007;Torres et al 2009). Similarly, in the present study, no differences in the prevalence of gene combinations were observed between the ulcer and non-ulcer patients for the ''triple-positive'' (vacA s1-cagA-babA2?)…”

Serum Levels of High-Sensitivity C-Reactive Protein (hs-CRP) in Helicobacter pylori-Infected Peptic Ulcer Patients and Its Association with Bacterial CagA Virulence Factor

“…strains [20]. Although results from many studies have shown CagA to be associated with a more severe inflammatory response and more severe pathological changes [17,18], results from some investigations have also demonstrated that expression of cytokines, including IL-6, IL-8, IL-10 and TNF-a, was not influenced by H. pylori virulence factors such as CagA [21][22][23][24]. Moreover, the polymorphisms in genes encoding some cytokines, for example IL-1, TNF-a and IFN-c, have been associated with H. pylori-induced gastric adenocarcinoma and peptic ulcers [25].…”