Immune evasion by proteolytic shedding of natural killer group 2, member D ligands in Helicobacter pylori infection
BackgroundHelicobacter pylori (H. pylori) uses various strategies that attenuate mucosal immunity to ensure its persistence in the stomach. We recently found evidence that H. pylori might modulate the natural killer group 2, member 2 (NKG2D) system. The NKG2D receptor and its ligands are a major act...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1282680/full |
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| author | Margit Anthofer Markus Windisch Rosa Haller Sandra Ehmann Sebastian Wrighton Michael Miller Lorenz Schernthanner Iris Kufferath Silvia Schauer Barbara Jelušić Sabine Kienesberger Sabine Kienesberger Ellen L. Zechner Ellen L. Zechner Gernot Posselt Mar Vales-Gomez Hugh T. Reyburn Gregor Gorkiewicz Gregor Gorkiewicz |
| author_facet | Margit Anthofer Markus Windisch Rosa Haller Sandra Ehmann Sebastian Wrighton Michael Miller Lorenz Schernthanner Iris Kufferath Silvia Schauer Barbara Jelušić Sabine Kienesberger Sabine Kienesberger Ellen L. Zechner Ellen L. Zechner Gernot Posselt Mar Vales-Gomez Hugh T. Reyburn Gregor Gorkiewicz Gregor Gorkiewicz |
| author_sort | Margit Anthofer |
| collection | DOAJ |
| description | BackgroundHelicobacter pylori (H. pylori) uses various strategies that attenuate mucosal immunity to ensure its persistence in the stomach. We recently found evidence that H. pylori 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 H. pylori infection.MethodsWe analyzed expression of NKG2D system genes in gastric tissues of H. pylori gastritis and gastric cancer patients, and performed cell-culture based infection experiments using H. pylori isogenic mutants and epithelial and NK cell lines.ResultsIn biopsies of H. pylori gastritis patients, NKG2D receptor expression was reduced while NKG2D ligands accumulated in the lamina propria, suggesting NKG2D evasion. In vitro, H. pylori induced the transcription and proteolytic shedding of NKG2D ligands in stomach epithelial cells, and these effects were associated with specific H. pylori virulence factors. The H. pylori-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.ConclusionH. pylori manipulates the NKG2D system. This so far unrecognized strategy of immune evasion by H. pylori 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. |
| first_indexed | 2024-03-08T12:30:18Z |
| format | Article |
| id | doaj.art-7eb6600bc12f45f996cdae771223c74f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T12:30:18Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7eb6600bc12f45f996cdae771223c74f2024-01-22T04:37:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011510.3389/fimmu.2024.12826801282680Immune evasion by proteolytic shedding of natural killer group 2, member D ligands in Helicobacter pylori infectionMargit Anthofer0Markus Windisch1Rosa Haller2Sandra Ehmann3Sebastian Wrighton4Michael Miller5Lorenz Schernthanner6Iris Kufferath7Silvia Schauer8Barbara Jelušić9Sabine Kienesberger10Sabine Kienesberger11Ellen L. Zechner12Ellen L. Zechner13Gernot Posselt14Mar Vales-Gomez15Hugh T. Reyburn16Gregor Gorkiewicz17Gregor Gorkiewicz18Institute of Pathology, Medical University of Graz, Graz, AustriaInstitute of Pathology, Medical University of Graz, Graz, AustriaInstitute of Pathology, Medical University of Graz, Graz, AustriaInstitute of Pathology, Medical University of Graz, Graz, AustriaInstitute of Pathology, Medical University of Graz, Graz, AustriaInstitute of Pathology, Medical University of Graz, Graz, AustriaInstitute of Pathology, Medical University of Graz, Graz, AustriaInstitute of Pathology, Medical University of Graz, Graz, AustriaInstitute of Pathology, Medical University of Graz, Graz, AustriaInstitute of Pathology, Medical University of Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaInteruniversity Cooperation, BioTechMed-Graz, Graz, AustriaInstitute of Molecular Biosciences, University of Graz, Graz, AustriaInteruniversity Cooperation, BioTechMed-Graz, Graz, AustriaDepartment of Biosciences and Medical Biology, Paris Lodron University of Salzburg, Salzburg, AustriaDepartment of Immunology and Oncology, Spanish National Centre for Biotechnology, Madrid, SpainDepartment of Immunology and Oncology, Spanish National Centre for Biotechnology, Madrid, SpainInstitute of Pathology, Medical University of Graz, Graz, AustriaInteruniversity Cooperation, BioTechMed-Graz, Graz, AustriaBackgroundHelicobacter pylori (H. pylori) uses various strategies that attenuate mucosal immunity to ensure its persistence in the stomach. We recently found evidence that H. pylori 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 H. pylori infection.MethodsWe analyzed expression of NKG2D system genes in gastric tissues of H. pylori gastritis and gastric cancer patients, and performed cell-culture based infection experiments using H. pylori isogenic mutants and epithelial and NK cell lines.ResultsIn biopsies of H. pylori gastritis patients, NKG2D receptor expression was reduced while NKG2D ligands accumulated in the lamina propria, suggesting NKG2D evasion. In vitro, H. pylori induced the transcription and proteolytic shedding of NKG2D ligands in stomach epithelial cells, and these effects were associated with specific H. pylori virulence factors. The H. pylori-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.ConclusionH. pylori manipulates the NKG2D system. This so far unrecognized strategy of immune evasion by H. pylori 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1282680/fullH. pyloriimmune evasionNK cellscytotoxic T cellsstomach cancertumor immunity |
| spellingShingle | Margit Anthofer Markus Windisch Rosa Haller Sandra Ehmann Sebastian Wrighton Michael Miller Lorenz Schernthanner Iris Kufferath Silvia Schauer Barbara Jelušić Sabine Kienesberger Sabine Kienesberger Ellen L. Zechner Ellen L. Zechner Gernot Posselt Mar Vales-Gomez Hugh T. Reyburn Gregor Gorkiewicz Gregor Gorkiewicz Immune evasion by proteolytic shedding of natural killer group 2, member D ligands in Helicobacter pylori infection Frontiers in Immunology H. pylori immune evasion NK cells cytotoxic T cells stomach cancer tumor immunity |
| title | Immune evasion by proteolytic shedding of natural killer group 2, member D ligands in Helicobacter pylori infection |
| title_full | Immune evasion by proteolytic shedding of natural killer group 2, member D ligands in Helicobacter pylori infection |
| title_fullStr | Immune evasion by proteolytic shedding of natural killer group 2, member D ligands in Helicobacter pylori infection |
| title_full_unstemmed | Immune evasion by proteolytic shedding of natural killer group 2, member D ligands in Helicobacter pylori infection |
| title_short | Immune evasion by proteolytic shedding of natural killer group 2, member D ligands in Helicobacter pylori infection |
| title_sort | immune evasion by proteolytic shedding of natural killer group 2 member d ligands in helicobacter pylori infection |
| topic | H. pylori immune evasion NK cells cytotoxic T cells stomach cancer tumor immunity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1282680/full |
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