Arginase 2 deletion leads to enhanced M1 macrophage activation and upregulated polyamine metabolism in response to Helicobacter pylori infection

Dana M. Hardbower, Mohammad Asim, Tracy Murray-Stewart, Robert A. Casero, Thomas Verriere, Nuruddeen D. Lewis, Rupesh Chaturvedi, M. Blanca Piazuelo, Keith T. Wilson

Research output: Contribution to journalArticlepeer-review

Abstract

We reported that arginase 2 (ARG2) deletion results in increased gastritis and decreased bacterial burden during Helicobacter pylori infection in mice. Our studies implicated a potential role for inducible nitric oxide (NO) synthase (NOS2), as Arg2−/− mice exhibited increased NOS2 levels in gastric macrophages, and NO can kill H. pylori. We now bred Arg2−/− to Nos2−/− mice, and infected them with H. pylori. Compared to wild-type mice, both Arg2−/− and Arg2−/−;Nos2−/− mice exhibited increased gastritis and decreased colonization, the latter indicating that the effect of ARG2 deletion on bacterial burden was not mediated by NO. While Arg2−/− mice demonstrated enhanced M1 macrophage activation, Nos2−/− and Arg2−/−;Nos2−/− mice did not demonstrate these changes, but exhibited increased CXCL1 and CXCL2 responses. There was an increased expression of the Th1/Th17 cytokines, interferon gamma and interleukin 17, in gastric tissues and splenic T-cells from Arg2−/−, but not Nos2−/− or Arg2−/−;Nos2−/− mice. Gastric tissues from infected Arg2−/− mice demonstrated increased expression of arginase 1, ornithine decarboxylase, adenosylmethionine decarboxylase 1, spermidine/spermine N1-acetyltransferase 1, and spermine oxidase, along with increased spermine levels. These data indicate that ARG2 deletion results in compensatory upregulation of gastric polyamine synthesis and catabolism during H. pylori infection, which may contribute to increased gastric inflammation and associated decreased bacterial load. Overall, the finding of this study is that ARG2 contributes to the immune evasion of H. pylori by restricting M1 macrophage activation and polyamine metabolism.

Original languageEnglish (US)
Pages (from-to)2375-2388
Number of pages14
JournalAmino Acids
Volume48
Issue number10
DOIs
StatePublished - Oct 1 2016

Keywords

  • Helicobacter pylori
  • Immune evasion
  • Macrophage activation
  • Polyamines

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

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