Helicobacter pylori SabA adhesin evokes a strong inflammatory response in human neutrophils which is down-regulated by the neutrophil-activating protein

Abstract

The human pathogen Helicobacter pylori expresses two dominant adhesins; the Lewis b blood group antigen binding adhesin, BabA, and the sialic acid-binding adhesin, SabA. These adhesins recognize specific carbohydrate moieties of the gastric epithelium, i.e. the Lewis b antigen, Le(b), and the sialyl-Lewis x antigen, sLe(x), respectively, which promote infection and inflammatory processes in the gastroduodenal tract. To assess the contribution of each of BabA, SabA and the neutrophil activating protein (HP-NAP) in a local inflammation, we investigated the traits of H. pylori mutants in their capacity to interact with and stimulate human neutrophils. We thence found that the SabA adhesin was not only the key inducer of oxidative metabolism (Unemo et al. J Biol Chem 280:15390-15397, 2005), but also essential in phagocytosis induction, as evaluated by flow cytometry, fluorescence microscopy and luminol-enhanced chemiluminescence. The napA deletion resulted in enhanced generation of reactive oxygen species and impaired adherence to the host cells. In conclusion, the SabA adhesin stimulates human neutrophils through selectin-mimicry. Interestingly, HP-NAP modulates the oxidative burst, which could tune the impact of the H. pylori infection for establishment of balanced and chronic inflammation of the gastric mucosa.

A Repetitive DNA Element Regulates Expression of the Helicobacter pylori Sialic Acid Binding Adhesin by a Rheostat-like Mechanism

“…SMI109 Δ hup was created by transformation of a Δ hup :: kan PCR fragment generated by hup-1 and hup-5 primers, and pAAG178 as template. SMI109 Δ napA was created by transformation of a Δ napA :: kan PCR fragment generated by napA1F and napA1R primers, and pBlue-Δ napA :: kan [78] as template. Deletion of the hup and napA genes was verified by PCR using hup-2 / hup-in and napA2F / napA2R primers, respectively.…”

Superoxide dismutase activity of Helicobacter pylori per se from 158 clinical isolates and the characteristics

“…BabA and SabA) have been shown to induce inflammatory cytokines (IL‐6, IL‐8, IL‐12, TNF‐α) and inflammatory cells in the stomach as the host immunoresponse. The inflamed tissue inevitably results in the production of various kinds of ROS, including O 2 − , which causes disorders through severe damage in the stomach (1–12). However, ROS potentially has a role in eliminating microorganisms to defend the cells and tissues in a type of host immunoreaction.…”

Higher Motility Enhances Bacterial Density and Inflammatory Response in Dyspeptic Patients Infected with Helicobacter pylori

“…In our previous study, we showed that the expression of SabA can enhance the bacterial density in the body when patients lack the BabA receptor, Le b antigen [21]. The binding of H. pylori to sialylated neutrophil receptors through SabA also plays a pivotal role in phagocytosis of the bacteria and the induction of the oxidative burst [28]. Therefore, this study further analyzed whether there is a synergistic effect of the presence of the SabA-sialyl-Le x interaction in the patients infected with different motility strains.…”