Arginase, Nitric Oxide, and the Defective Immune Response to Helicobacter pylori

Abstract

Helicobacter pylori infection persists for the life of the host due to the failure of the immune response to eradicate the bacterium. Determining the mechanisms by which the bacterium escapes the immune response are clinically important. Our aim was to determine if induction of arginase II (Arg2) by H. pylori modulates host defense. We have demonstrated that macrophage nitric oxide production can kill H. pylori; however, induction of macrophage Arg2 inhibits inducible nitric oxide synthase (iNOS) translation, induces apoptosis, and restricts bacterial killing. After 4 mo infection with H. pylori, we found that enhanced gastritis correlated with decreased bacterial colonization in Arg2–/– mice, but not WT mice. We found that iNOS+ macrophages were more abundant in Arg2–/– mice, less apoptotic, and had increased nitrotyrosine staining. This correlated with enhanced pro-inflammatory cytokine production. These studies suggest that Arg2 mediates the immune evasion of H. pylori by restricting macrophage function.