Immune evasion by proteolytic shedding of natural killer group 2, member D ligands in infection.

Background: () uses various strategies that attenuate mucosal immunity to ensure its persistence in the stomach. We recently found evidence that might modulate the natural killer group 2, member 2 (NKG2D) system. The NKG2D receptor and its ligands are a major activation system of natural killer and cytotoxic T cells, which are important for mucosal immunity and tumor immunosurveillance. The NKG2D system allows recognition and elimination of infected and transformed cells, however viruses and cancers often subvert its activation. Here we aimed to identify a potential evasion of the NKG2D system in infection.

Methods: We analyzed expression of NKG2D system genes in gastric tissues of gastritis and gastric cancer patients, and performed cell-culture based infection experiments using isogenic mutants and epithelial and NK cell lines.

Results: In biopsies of gastritis patients, NKG2D receptor expression was reduced while NKG2D ligands accumulated in the lamina propria, suggesting NKG2D evasion. , induced the transcription and proteolytic shedding of NKG2D ligands in stomach epithelial cells, and these effects were associated with specific virulence factors. The -driven release of soluble NKG2D ligands reduced the immunogenic visibility of infected cells and attenuated the cytotoxic activity of effector immune cells, specifically the anti-tumor activity of NK cells.

Conclusion: manipulates the NKG2D system. This so far unrecognized strategy of immune evasion by could potentially facilitate chronic bacterial persistence and might also promote stomach cancer development by allowing transformed cells to escape immune recognition and grow unimpeded to overt malignancy.