Research ArticleMICROBIOLOGY

Helicobacter pylori–induced matrix metallopeptidase-10 promotes gastric bacterial colonization and gastritis

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Science Advances  03 Apr 2019:
Vol. 5, no. 4, eaau6547
DOI: 10.1126/sciadv.aau6547

Abstract

The interaction between gastric epithelium and immune response plays key roles in H. pylori–associated pathology. We demonstrated a procolonization and proinflammation role of MMP-10 in H. pylori infection. MMP-10 is elevated in gastric mucosa and is produced by gastric epithelial cells synergistically induced by H. pylori and IL-22 via the ERK pathway. Human gastric MMP-10 was correlated with H. pylori colonization and the severity of gastritis, and mouse MMP-10 from non–BM-derived cells promoted bacteria colonization and inflammation. H. pylori colonization and inflammation were attenuated in IL-22−/−, MMP-10−/−, and IL-22−/−MMP-10−/− mice. MMP-10–associated inflammation is characterized by the influx of CD8+ T cells, whose migration is induced via MMP-10–CXCL16 axis by gastric epithelial cells. Under the influence of MMP-10, Reg3a, E-cadherin, and zonula occludens–1 proteins decrease, resulting in impaired host defense and increased H. pylori colonization. Our results suggest that MMP-10 facilitates H. pylori persistence and promotes gastritis.

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