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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694194/ http://dx.doi.org/10.3389/fimmu.2023.1290833 |
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author | Frauenlob, Tobias Neuper, Theresa Regl, Christof Schaepertoens, Veronika Unger, Michael S. Oswald, Anna-Lena Dang, Hieu-Hoa Huber, Christian G. Aberger, Fritz Wessler, Silja Horejs-Hoeck, Jutta |
author_facet | Frauenlob, Tobias Neuper, Theresa Regl, Christof Schaepertoens, Veronika Unger, Michael S. Oswald, Anna-Lena Dang, Hieu-Hoa Huber, Christian G. Aberger, Fritz Wessler, Silja Horejs-Hoeck, Jutta |
author_sort | Frauenlob, Tobias |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-10694194 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106941942023-12-05 Helicobacter pylori induces a novel form of innate immune memory via accumulation of NF-кB proteins Frauenlob, Tobias Neuper, Theresa Regl, Christof Schaepertoens, Veronika Unger, Michael S. Oswald, Anna-Lena Dang, Hieu-Hoa Huber, Christian G. Aberger, Fritz Wessler, Silja Horejs-Hoeck, Jutta Front Immunol Immunology 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. Frontiers Media S.A. 2023-11-20 /pmc/articles/PMC10694194/ http://dx.doi.org/10.3389/fimmu.2023.1290833 Text en Copyright © 2023 Frauenlob, Neuper, Regl, Schaepertoens, Unger, Oswald, Dang, Huber, Aberger, Wessler and Horejs-Hoeck https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Frauenlob, Tobias Neuper, Theresa Regl, Christof Schaepertoens, Veronika Unger, Michael S. Oswald, Anna-Lena Dang, Hieu-Hoa Huber, Christian G. Aberger, Fritz Wessler, Silja Horejs-Hoeck, Jutta Helicobacter pylori induces a novel form of innate immune memory via accumulation of NF-кB proteins |
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 | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694194/ http://dx.doi.org/10.3389/fimmu.2023.1290833 |
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