Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694194/
http://dx.doi.org/10.3389/fimmu.2023.1290833
_version_ 1785153320321548288
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
work_keys_str_mv AT frauenlobtobias helicobacterpyloriinducesanovelformofinnateimmunememoryviaaccumulationofnfkbproteins
AT neupertheresa helicobacterpyloriinducesanovelformofinnateimmunememoryviaaccumulationofnfkbproteins
AT reglchristof helicobacterpyloriinducesanovelformofinnateimmunememoryviaaccumulationofnfkbproteins
AT schaepertoensveronika helicobacterpyloriinducesanovelformofinnateimmunememoryviaaccumulationofnfkbproteins
AT ungermichaels helicobacterpyloriinducesanovelformofinnateimmunememoryviaaccumulationofnfkbproteins
AT oswaldannalena helicobacterpyloriinducesanovelformofinnateimmunememoryviaaccumulationofnfkbproteins
AT danghieuhoa helicobacterpyloriinducesanovelformofinnateimmunememoryviaaccumulationofnfkbproteins
AT huberchristiang helicobacterpyloriinducesanovelformofinnateimmunememoryviaaccumulationofnfkbproteins
AT abergerfritz helicobacterpyloriinducesanovelformofinnateimmunememoryviaaccumulationofnfkbproteins
AT wesslersilja helicobacterpyloriinducesanovelformofinnateimmunememoryviaaccumulationofnfkbproteins
AT horejshoeckjutta helicobacterpyloriinducesanovelformofinnateimmunememoryviaaccumulationofnfkbproteins