TheHelicobacter pyloriBlood Group Antigen-Binding Adhesin Facilitates Bacterial Colonization and Augments a Nonspecific Immune Response

Abstract

Presence of the Helicobacter pylori adherence factor blood group Ag-binding adhesin (BabA; binding to Lewisb (Leb)) is associated with ulcer disease, adenocarcinoma, and precancerous lesions. The importance of BabA for bacterial colonization and the inflammatory response is unknown. A total of 141 antral biopsies from H. pylori-infected patients were assessed in regard to the degree of granulocytic (G0°–G3°) and lymphocytic (L1°–L3°) infiltration. DNA genotypes of babA2 (the transcriptionally active gene of BabA), cagA, and vacAs1/2 were determined by PCR. Colonization density and Leb status on gastric epithelial cells were determined by immunohistochemistry. Real-time quantitative (TaqMan) RT-PCR determined mRNA expression of IL-8, TNF -α, and the Th1 markers IFN-γ and the IL-12R β2 chain. A total of 91% of infected patients were Leb positive. The vacAs1+/cagA+ strains harboring babA2 showed significantly higher levels of granulocytic infiltration, bacterial colonization, and IL-8 mRNA than vacAs1+/cagA+ strains lacking babA2. IL-8 mRNA and protein production by KATO III cells in vitro increased dose dependently with addition of different numbers of type 1 strains (G27 and 2808 strains, 0.1–20 bacteria/cell). The mRNA expression of TNF-α, IFN-γ, and IL-12R β2 was higher in H. pylori-positive patients than in controls, but it did not differ significantly between patients infected with different strain types. These data suggest that BabA facilitates colonization of H. pylori and thereby increases IL-8 response, resulting in enhanced mucosal inflammation. Infection with strains harboring BabA thereby augment a nonspecific immune response, whereas the Th1 response toward H. pylori appears to be independent of BabA, cytotoxin-associated gene A, or vacuolating cytotoxin.

Structure of the human gastric bacterial community in relation to Helicobacter pylori status

“…H. pylori presence affects the gastric environment, hormones and immunity (Atherton and Blaser, 2009). The bacterium promotes density-dependent humoral and cellular immune responses (Plebani et al, 1996), which might affect homeostasis of leptin (Nishi et al, 2005;Pacifico et al, 2008), a hormone that modulates immunity and gastric acid secretion and promotes a Th1 response (Faggioni et al, 2001;Perry et al, 2010) The intimate contact of H. pylori with epithelial cells (through adhesin molecules such as BabA or through Cag PAI proteins) augments immune responses (Rad et al, 2002), presence of inflammatory cells (Atherton et al, 1997;Bodger and Crabtree, 1998) and cytokines (IL-1b, -2, -6, -8 and TNF-a) (Yamaoka et al, 1997), which also might affect other bacterial species. More research is needed to characterize the physiological differences related to H. pylori status, including variation in the gastric microbiota, as well as its clinical implications.…”

Roles of Helicobacter pylori BabA in gastroduodenal pathogenesis

“…Most previous studies evaluating BabA (babA) status have used PCR techniques based on detection of the 10 bp deletion to distinguish between the babA2 and babA1 genes ( Table 2) [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] . However, as described above, strains carrying the prototypical silent babA1 gene are very rare, and in addition, the BabA protein levels often do not match the presence of the babA (babA2) gene [31] .…”

Helicobacter pylori BabA Expression, Gastric Mucosal Injury, and Clinical Outcome

“…babA status (babA2 positive or negative) was determined by PCR using primer pairs and amplification conditions previously described (Figure 1). [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Most of these primers were designed to detect the 10-bp signal sequence deletion of babA1, which is absent in babA2. Most previous studies used primer pair A (babA2S and babA2AS) ( Table 1) in which 2 nucleotides of the forward primer were changed from the known sequences of the babA2 gene from strain CCUG17875 (ie, AC to GT) ( Figure 1).…”

“…3 Most studies evaluating BabA status have used polymerase chain reaction (PCR) techniques based on detection of the 10-bp deletion to distinguish between the babA2 and babA1 genes ( Table 1). [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] However, the ability of such PCR-based strategies to detect the presence of a functional babA gene is questionable. For example, H pylori strains unable to bind to Lewis b antigen (Le b ) have been reported to contain signal peptide sequences that are identical to those of strains with a functional babA2 gene (eg, strain 26695).…”