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

Abstract

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. 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. 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 3months, this antibody was readily detected in both sera and gastric tissues 5days 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. SOD from H.pylori can inhibit the production of pro-inflammatory cytokine during in vivo infection.