Immune evasion by proteolytic shedding of natural killer group 2, member D ligands in Helicobacter pylori infection
Copyright © 2024 Anthofer, Windisch, Haller, Ehmann, Wrighton, Miller, Schernthanner, Kufferath, Schauer, Jelušić, Kienesberger, Zechner, Posselt, Vales-Gomez, Reyburn and Gorkiewicz..
Background: Helicobacter 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.
Methods: We 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.
Results: In 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.
Conclusion: H. 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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Frontiers in immunology - 15(2024) vom: 01., Seite 1282680 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Anthofer, Margit [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 07.02.2024 Date Revised 27.03.2024 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.3389/fimmu.2024.1282680 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368074536 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368074536 | ||
| 003 | DE-627 | ||
| 005 | 20240327235741.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240206s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3389/fimmu.2024.1282680 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1351.xml |
| 035 | |a (DE-627)NLM368074536 | ||
| 035 | |a (NLM)38318189 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Anthofer, Margit |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Immune evasion by proteolytic shedding of natural killer group 2, member D ligands in Helicobacter pylori infection |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 07.02.2024 | ||
| 500 | |a Date Revised 27.03.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 Anthofer, Windisch, Haller, Ehmann, Wrighton, Miller, Schernthanner, Kufferath, Schauer, Jelušić, Kienesberger, Zechner, Posselt, Vales-Gomez, Reyburn and Gorkiewicz. | ||
| 520 | |a Background: Helicobacter 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 | ||
| 520 | |a Methods: We 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 | ||
| 520 | |a Results: In 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 | ||
| 520 | |a Conclusion: H. 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a H. pylori | |
| 650 | 4 | |a NK cells | |
| 650 | 4 | |a NKG2D (natural killer group 2 member D) | |
| 650 | 4 | |a cytotoxic T cells | |
| 650 | 4 | |a immune evasion | |
| 650 | 4 | |a stomach cancer | |
| 650 | 4 | |a stomach microbiota | |
| 650 | 4 | |a tumor immunity | |
| 650 | 7 | |a NK Cell Lectin-Like Receptor Subfamily K |2 NLM | |
| 650 | 7 | |a Peptide Hydrolases |2 NLM | |
| 650 | 7 | |a EC 3.4.- |2 NLM | |
| 700 | 1 | |a Windisch, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Haller, Rosa |e verfasserin |4 aut | |
| 700 | 1 | |a Ehmann, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a Wrighton, Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Schernthanner, Lorenz |e verfasserin |4 aut | |
| 700 | 1 | |a Kufferath, Iris |e verfasserin |4 aut | |
| 700 | 1 | |a Schauer, Silvia |e verfasserin |4 aut | |
| 700 | 1 | |a Jelušić, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Kienesberger, Sabine |e verfasserin |4 aut | |
| 700 | 1 | |a Zechner, Ellen L |e verfasserin |4 aut | |
| 700 | 1 | |a Posselt, Gernot |e verfasserin |4 aut | |
| 700 | 1 | |a Vales-Gomez, Mar |e verfasserin |4 aut | |
| 700 | 1 | |a Reyburn, Hugh T |e verfasserin |4 aut | |
| 700 | 1 | |a Gorkiewicz, Gregor |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Frontiers in immunology |d 2010 |g 15(2024) vom: 01., Seite 1282680 |w (DE-627)NLM215811453 |x 1664-3224 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2024 |g day:01 |g pages:1282680 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3389/fimmu.2024.1282680 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2024 |b 01 |h 1282680 | ||