<i>Helicobacter pylori</i>-induced matrix metallopeptidase-10 promotes gastric bacterial colonization and gastritis.

Abstract

The interaction between gastric epithelium and immune response plays key roles in <i>H. pylori</i>-associated pathology. We demonstrated a procolonization and proinflammation role of MMP-10 in <i>H. pylori</i> infection. MMP-10 is elevated in gastric mucosa and is produced by gastric epithelial cells synergistically induced by <i>H. pylori</i> and IL-22 via the ERK pathway. Human gastric MMP-10 was correlated with <i>H. pylori</i> colonization and the severity of gastritis, and mouse MMP-10 from non-BM-derived cells promoted bacteria colonization and inflammation. <i>H. pylori</i> 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 <i>H. pylori</i> colonization. Our results suggest that MMP-10 facilitates <i>H. pylori</i> persistence and promotes gastritis.