Helicobacter pylori induces a novel form of innate immune memory via accumulation of NF-кB proteins
Helicobacter pylori is a widespread Gram-negative pathogen involved in a variety of gastrointestinal diseases, including gastritis, ulceration, mucosa-associated lymphoid tissue (MALT) lymphoma and gastric cancer. Immune responses aimed at eradication of H. pylori often prove futile, and paradoxical...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1290833/full |
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| author | Tobias Frauenlob Tobias Frauenlob Tobias Frauenlob Theresa Neuper Theresa Neuper Christof Regl Veronika Schaepertoens Veronika Schaepertoens Michael S. Unger Michael S. Unger Anna-Lena Oswald Hieu-Hoa Dang Hieu-Hoa Dang Hieu-Hoa Dang Christian G. Huber Christian G. Huber Christian G. Huber Fritz Aberger Fritz Aberger Fritz Aberger Silja Wessler Silja Wessler Silja Wessler Jutta Horejs-Hoeck Jutta Horejs-Hoeck Jutta Horejs-Hoeck |
| author_facet | Tobias Frauenlob Tobias Frauenlob Tobias Frauenlob Theresa Neuper Theresa Neuper Christof Regl Veronika Schaepertoens Veronika Schaepertoens Michael S. Unger Michael S. Unger Anna-Lena Oswald Hieu-Hoa Dang Hieu-Hoa Dang Hieu-Hoa Dang Christian G. Huber Christian G. Huber Christian G. Huber Fritz Aberger Fritz Aberger Fritz Aberger Silja Wessler Silja Wessler Silja Wessler Jutta Horejs-Hoeck Jutta Horejs-Hoeck Jutta Horejs-Hoeck |
| author_sort | Tobias Frauenlob |
| collection | DOAJ |
| description | Helicobacter pylori is a widespread Gram-negative pathogen involved in a variety of gastrointestinal diseases, including gastritis, ulceration, mucosa-associated lymphoid tissue (MALT) lymphoma and gastric cancer. Immune responses aimed at eradication of H. pylori often prove futile, and paradoxically play a crucial role in the degeneration of epithelial integrity and disease progression. We have previously shown that H. pylori infection of primary human monocytes increases their potential to respond to subsequent bacterial stimuli – a process that may be involved in the generation of exaggerated, yet ineffective immune responses directed against the pathogen. In this study, we show that H. pylori-induced monocyte priming is not a common feature of Gram-negative bacteria, as Acinetobacter lwoffii induces tolerance to subsequent Escherichia coli lipopolysaccharide (LPS) challenge. Although the increased reactivity of H. pylori-infected monocytes seems to be specific to H. pylori, it appears to be independent of its virulence factors Cag pathogenicity island (CagPAI), cytotoxin associated gene A (CagA), vacuolating toxin A (VacA) and γ-glutamyl transferase (γ-GT). Utilizing whole-cell proteomics complemented with biochemical signaling studies, we show that H. pylori infection of monocytes induces a unique proteomic signature compared to other pro-inflammatory priming stimuli, namely LPS and the pathobiont A. lwoffii. Contrary to these tolerance-inducing stimuli, H. pylori priming leads to accumulation of NF-кB proteins, including p65/RelA, and thus to the acquisition of a monocyte phenotype more responsive to subsequent LPS challenge. The plasticity of pro-inflammatory responses based on abundance and availability of intracellular signaling molecules may be a heretofore underappreciated form of regulating innate immune memory as well as a novel facet of the pathobiology induced by H. pylori. |
| first_indexed | 2024-03-10T18:59:36Z |
| format | Article |
| id | doaj.art-cb89368a84c4480bafb6c997f752a220 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-10T18:59:36Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-cb89368a84c4480bafb6c997f752a2202023-11-20T04:32:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-11-011410.3389/fimmu.2023.12908331290833Helicobacter pylori induces a novel form of innate immune memory via accumulation of NF-кB proteinsTobias Frauenlob0Tobias Frauenlob1Tobias Frauenlob2Theresa Neuper3Theresa Neuper4Christof Regl5Veronika Schaepertoens6Veronika Schaepertoens7Michael S. Unger8Michael S. Unger9Anna-Lena Oswald10Hieu-Hoa Dang11Hieu-Hoa Dang12Hieu-Hoa Dang13Christian G. Huber14Christian G. Huber15Christian G. Huber16Fritz Aberger17Fritz Aberger18Fritz Aberger19Silja Wessler20Silja Wessler21Silja Wessler22Jutta Horejs-Hoeck23Jutta Horejs-Hoeck24Jutta Horejs-Hoeck25Department of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaCancer Cluster Salzburg (CCS), Salzburg, AustriaCenter for Tumorbiology and Immunology (CTBI), University of Salzburg, Salzburg, AustriaDepartment of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaCenter for Tumorbiology and Immunology (CTBI), University of Salzburg, Salzburg, AustriaDepartment of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaDepartment of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaCenter for Tumorbiology and Immunology (CTBI), University of Salzburg, Salzburg, AustriaDepartment of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaCenter for Tumorbiology and Immunology (CTBI), University of Salzburg, Salzburg, AustriaDepartment of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaDepartment of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaCancer Cluster Salzburg (CCS), Salzburg, AustriaCenter for Tumorbiology and Immunology (CTBI), University of Salzburg, Salzburg, AustriaDepartment of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaCancer Cluster Salzburg (CCS), Salzburg, AustriaCenter for Tumorbiology and Immunology (CTBI), University of Salzburg, Salzburg, AustriaDepartment of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaCancer Cluster Salzburg (CCS), Salzburg, AustriaCenter for Tumorbiology and Immunology (CTBI), University of Salzburg, Salzburg, AustriaDepartment of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaCancer Cluster Salzburg (CCS), Salzburg, AustriaCenter for Tumorbiology and Immunology (CTBI), University of Salzburg, Salzburg, AustriaDepartment of Biosciences and Medical Biology, University of Salzburg, Salzburg, AustriaCancer Cluster Salzburg (CCS), Salzburg, AustriaCenter for Tumorbiology and Immunology (CTBI), University of Salzburg, Salzburg, AustriaHelicobacter pylori is a widespread Gram-negative pathogen involved in a variety of gastrointestinal diseases, including gastritis, ulceration, mucosa-associated lymphoid tissue (MALT) lymphoma and gastric cancer. Immune responses aimed at eradication of H. pylori often prove futile, and paradoxically play a crucial role in the degeneration of epithelial integrity and disease progression. We have previously shown that H. pylori infection of primary human monocytes increases their potential to respond to subsequent bacterial stimuli – a process that may be involved in the generation of exaggerated, yet ineffective immune responses directed against the pathogen. In this study, we show that H. pylori-induced monocyte priming is not a common feature of Gram-negative bacteria, as Acinetobacter lwoffii induces tolerance to subsequent Escherichia coli lipopolysaccharide (LPS) challenge. Although the increased reactivity of H. pylori-infected monocytes seems to be specific to H. pylori, it appears to be independent of its virulence factors Cag pathogenicity island (CagPAI), cytotoxin associated gene A (CagA), vacuolating toxin A (VacA) and γ-glutamyl transferase (γ-GT). Utilizing whole-cell proteomics complemented with biochemical signaling studies, we show that H. pylori infection of monocytes induces a unique proteomic signature compared to other pro-inflammatory priming stimuli, namely LPS and the pathobiont A. lwoffii. Contrary to these tolerance-inducing stimuli, H. pylori priming leads to accumulation of NF-кB proteins, including p65/RelA, and thus to the acquisition of a monocyte phenotype more responsive to subsequent LPS challenge. The plasticity of pro-inflammatory responses based on abundance and availability of intracellular signaling molecules may be a heretofore underappreciated form of regulating innate immune memory as well as a novel facet of the pathobiology induced by H. pylori.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1290833/fullH. pyloritrained immunityinnate immune memoryNF-кBinnate immunitytolerance |
| spellingShingle | Tobias Frauenlob Tobias Frauenlob Tobias Frauenlob Theresa Neuper Theresa Neuper Christof Regl Veronika Schaepertoens Veronika Schaepertoens Michael S. Unger Michael S. Unger Anna-Lena Oswald Hieu-Hoa Dang Hieu-Hoa Dang Hieu-Hoa Dang Christian G. Huber Christian G. Huber Christian G. Huber Fritz Aberger Fritz Aberger Fritz Aberger Silja Wessler Silja Wessler Silja Wessler Jutta Horejs-Hoeck Jutta Horejs-Hoeck Jutta Horejs-Hoeck Helicobacter pylori induces a novel form of innate immune memory via accumulation of NF-кB proteins Frontiers in Immunology H. pylori trained immunity innate immune memory NF-кB innate immunity tolerance |
| title | Helicobacter pylori induces a novel form of innate immune memory via accumulation of NF-кB proteins |
| title_full | Helicobacter pylori induces a novel form of innate immune memory via accumulation of NF-кB proteins |
| title_fullStr | Helicobacter pylori induces a novel form of innate immune memory via accumulation of NF-кB proteins |
| title_full_unstemmed | Helicobacter pylori induces a novel form of innate immune memory via accumulation of NF-кB proteins |
| title_short | Helicobacter pylori induces a novel form of innate immune memory via accumulation of NF-кB proteins |
| title_sort | helicobacter pylori induces a novel form of innate immune memory via accumulation of nf кb proteins |
| topic | H. pylori trained immunity innate immune memory NF-кB innate immunity tolerance |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1290833/full |
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