Cargando…
Helicobacter pylori binds human Annexins via Lipopolysaccharide to interfere with Toll-like Receptor 4 signaling
Helicobacter pylori colonizes half of the global population and causes gastritis, peptic ulcer disease or gastric cancer. In this study, we were interested in human annexin (ANX), which comprises a protein family with diverse and partly unknown physiological functions, but with a potential role in m...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8890734/ https://www.ncbi.nlm.nih.gov/pubmed/35176125 http://dx.doi.org/10.1371/journal.ppat.1010326 |
_version_ | 1784661708695928832 |
---|---|
author | Schmidinger, Barbara Petri, Kristina Lettl, Clara Li, Hong Namineni, Sukumar Ishikawa-Ankerhold, Hellen Jiménez-Soto, Luisa Fernanda Haas, Rainer |
author_facet | Schmidinger, Barbara Petri, Kristina Lettl, Clara Li, Hong Namineni, Sukumar Ishikawa-Ankerhold, Hellen Jiménez-Soto, Luisa Fernanda Haas, Rainer |
author_sort | Schmidinger, Barbara |
collection | PubMed |
description | Helicobacter pylori colonizes half of the global population and causes gastritis, peptic ulcer disease or gastric cancer. In this study, we were interested in human annexin (ANX), which comprises a protein family with diverse and partly unknown physiological functions, but with a potential role in microbial infections and possible involvement in gastric cancer. We demonstrate here for the first time that H. pylori is able to specifically bind ANXs. Binding studies with purified H. pylori LPS and specific H. pylori LPS mutant strains indicated binding of ANXA5 to lipid A, which was dependent on the lipid A phosphorylation status. Remarkably, ANXA5 binding almost completely inhibited LPS-mediated Toll-like receptor 4- (TLR4) signaling in a TLR4-specific reporter cell line. Furthermore, the interaction is relevant for gastric colonization, as a mouse-adapted H. pylori increased its ANXA5 binding capacity after gastric passage and its ANXA5 incubation in vitro interfered with TLR4 signaling. Moreover, both ANXA2 and ANXA5 levels were upregulated in H. pylori-infected human gastric tissue, and H. pylori can be found in close association with ANXs in the human stomach. Furthermore, an inhibitory effect of ANXA5 binding for CagA translocation could be confirmed. Taken together, our results highlight an adaptive ability of H. pylori to interact with the host cell factor ANX potentially dampening innate immune recognition. |
format | Online Article Text |
id | pubmed-8890734 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-88907342022-03-03 Helicobacter pylori binds human Annexins via Lipopolysaccharide to interfere with Toll-like Receptor 4 signaling Schmidinger, Barbara Petri, Kristina Lettl, Clara Li, Hong Namineni, Sukumar Ishikawa-Ankerhold, Hellen Jiménez-Soto, Luisa Fernanda Haas, Rainer PLoS Pathog Research Article Helicobacter pylori colonizes half of the global population and causes gastritis, peptic ulcer disease or gastric cancer. In this study, we were interested in human annexin (ANX), which comprises a protein family with diverse and partly unknown physiological functions, but with a potential role in microbial infections and possible involvement in gastric cancer. We demonstrate here for the first time that H. pylori is able to specifically bind ANXs. Binding studies with purified H. pylori LPS and specific H. pylori LPS mutant strains indicated binding of ANXA5 to lipid A, which was dependent on the lipid A phosphorylation status. Remarkably, ANXA5 binding almost completely inhibited LPS-mediated Toll-like receptor 4- (TLR4) signaling in a TLR4-specific reporter cell line. Furthermore, the interaction is relevant for gastric colonization, as a mouse-adapted H. pylori increased its ANXA5 binding capacity after gastric passage and its ANXA5 incubation in vitro interfered with TLR4 signaling. Moreover, both ANXA2 and ANXA5 levels were upregulated in H. pylori-infected human gastric tissue, and H. pylori can be found in close association with ANXs in the human stomach. Furthermore, an inhibitory effect of ANXA5 binding for CagA translocation could be confirmed. Taken together, our results highlight an adaptive ability of H. pylori to interact with the host cell factor ANX potentially dampening innate immune recognition. Public Library of Science 2022-02-17 /pmc/articles/PMC8890734/ /pubmed/35176125 http://dx.doi.org/10.1371/journal.ppat.1010326 Text en © 2022 Schmidinger et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Schmidinger, Barbara Petri, Kristina Lettl, Clara Li, Hong Namineni, Sukumar Ishikawa-Ankerhold, Hellen Jiménez-Soto, Luisa Fernanda Haas, Rainer Helicobacter pylori binds human Annexins via Lipopolysaccharide to interfere with Toll-like Receptor 4 signaling |
title | Helicobacter pylori binds human Annexins via Lipopolysaccharide to interfere with Toll-like Receptor 4 signaling |
title_full | Helicobacter pylori binds human Annexins via Lipopolysaccharide to interfere with Toll-like Receptor 4 signaling |
title_fullStr | Helicobacter pylori binds human Annexins via Lipopolysaccharide to interfere with Toll-like Receptor 4 signaling |
title_full_unstemmed | Helicobacter pylori binds human Annexins via Lipopolysaccharide to interfere with Toll-like Receptor 4 signaling |
title_short | Helicobacter pylori binds human Annexins via Lipopolysaccharide to interfere with Toll-like Receptor 4 signaling |
title_sort | helicobacter pylori binds human annexins via lipopolysaccharide to interfere with toll-like receptor 4 signaling |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8890734/ https://www.ncbi.nlm.nih.gov/pubmed/35176125 http://dx.doi.org/10.1371/journal.ppat.1010326 |
work_keys_str_mv | AT schmidingerbarbara helicobacterpyloribindshumanannexinsvialipopolysaccharidetointerferewithtolllikereceptor4signaling AT petrikristina helicobacterpyloribindshumanannexinsvialipopolysaccharidetointerferewithtolllikereceptor4signaling AT lettlclara helicobacterpyloribindshumanannexinsvialipopolysaccharidetointerferewithtolllikereceptor4signaling AT lihong helicobacterpyloribindshumanannexinsvialipopolysaccharidetointerferewithtolllikereceptor4signaling AT naminenisukumar helicobacterpyloribindshumanannexinsvialipopolysaccharidetointerferewithtolllikereceptor4signaling AT ishikawaankerholdhellen helicobacterpyloribindshumanannexinsvialipopolysaccharidetointerferewithtolllikereceptor4signaling AT jimenezsotoluisafernanda helicobacterpyloribindshumanannexinsvialipopolysaccharidetointerferewithtolllikereceptor4signaling AT haasrainer helicobacterpyloribindshumanannexinsvialipopolysaccharidetointerferewithtolllikereceptor4signaling |