Superoxide dismutase from Helicobacter pylori suppresses the production of pro-inflammatory cytokines during in vivo infection.

BACKGROUND: Helicobacter pylori has undergone considerable adaptation to allow chronic persistence within the gastric environment. While H. pylori-associated diseases are driven by an excessive inflammation, severe gastritis is detrimental to colonization by this pathogen. Hence, H. pylori has developed strategies to minimize the severity of gastritis it triggers in its host. Superoxide dismutase (SOD) is well known for its role in protecting against oxidative attack; less recognized is its ability to inhibit immunity, shown for SOD from mammalian sources and those of some bacterial species. This study examined whether H. pylori SOD (HpSOD) has the ability to inhibit the host immune response to these bacteria. MATERIALS AND METHODS: The ability of recombinant HpSOD to modify the response to LPS was measured using mouse macrophages. A monoclonal antibody against HpSOD was generated and injected into H. pylori-infected mice. RESULTS: Addition of HpSOD to cultures of mouse macrophages significantly inhibited the pro-inflammatory cytokine response to LPS stimulation. A monoclonal antibody was generated that was specific for SOD from H. pylori. When injected into mice infected with H. pylori for 3 months, this antibody was readily detected in both sera and gastric tissues 5 days later. While treatment with anti-HpSOD had no effect on H. pylori colonization at this time point, it significantly increased the levels of a range of pro-inflammatory cytokines in the gastric tissues. This did not occur with antibodies against other antioxidant enzymes. CONCLUSIONS: SOD from H. pylori can inhibit the production of pro-inflammatory cytokine during in vivo infection.

Helicobacter pylori thiolperoxidase as a protective antigen in single- and multi-component vaccines.

Helicobacter pylori is an important pathogen of the human stomach, and the development of a protective vaccine has been an enticing goal for many years. The H. pylori antioxidant enzymes superoxide dismutase (SOD) and catalase (KatA) have been shown to be protective as vaccine antigens in mice, demonstrating that the organism's antioxidant enzyme system is a fruitful target for vaccine development. The research described here demonstrates that an additional antioxidant enzyme, thiolperoxidase (Tpx), is effective as a prophylactic vaccine antigen via both systemic and mucosal routes. The functional relationship between SOD, KatA and Tpx also provided an opportunity to investigate synergistic or additive effects when the three antigens were used in combination. Although the antigens still provided equivalent protection when administered in combination, no additional protection was observed. Moreover a decrease in antibody titres to the individual antigens was observed when delivered in combination via the nasal route, though not when injected subcutaneously. The findings of this paper demonstrate that the antioxidant system of H. pylori presents a particularly rich resource for vaccine development.