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Helicobacter pylori actively suppresses innate immune nucleic acid receptors

Chronic mucosal pathogens have evolved multiple strategies to manipulate the host immune response; consequently, microbes contribute to the development of >2 million cases of cancer/year. Gastric adenocarcinoma is the fourth leading cause of cancer-related death and Helicobacter pylori confers th...

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Autores principales: Dooyema, Samuel D.R., Noto, Jennifer M., Wroblewski, Lydia E., Piazuelo, M. Blanca, Krishna, Uma, Suarez, Giovanni, Romero-Gallo, Judith, Delgado, Alberto G., Peek, Richard M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9341374/
https://www.ncbi.nlm.nih.gov/pubmed/35905376
http://dx.doi.org/10.1080/19490976.2022.2105102
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author Dooyema, Samuel D.R.
Noto, Jennifer M.
Wroblewski, Lydia E.
Piazuelo, M. Blanca
Krishna, Uma
Suarez, Giovanni
Romero-Gallo, Judith
Delgado, Alberto G.
Peek, Richard M.
author_facet Dooyema, Samuel D.R.
Noto, Jennifer M.
Wroblewski, Lydia E.
Piazuelo, M. Blanca
Krishna, Uma
Suarez, Giovanni
Romero-Gallo, Judith
Delgado, Alberto G.
Peek, Richard M.
author_sort Dooyema, Samuel D.R.
collection PubMed
description Chronic mucosal pathogens have evolved multiple strategies to manipulate the host immune response; consequently, microbes contribute to the development of >2 million cases of cancer/year. Gastric adenocarcinoma is the fourth leading cause of cancer-related death and Helicobacter pylori confers the highest risk for this disease. Gastric innate immune effectors can either eliminate bacteria or mobilize adaptive immune responses including Toll-like receptors (TLRs), and cytosolic DNA sensor/adaptor proteins (e.g., stimulator of interferon genes, STING). The H. pylori strain-specific cag type IV secretion system (T4SS) augments gastric cancer risk and translocates DNA into epithelial cells where it activates the microbial DNA sensor TLR9 and suppresses injury in vivo; however, the ability of H. pylori to suppress additional nucleic acid PRRs within the context of chronic gastric inflammation and injury remains undefined. In this study, in vitro and ex vivo experiments identified a novel mechanism through which H. pylori actively suppresses STING and RIG-I signaling via downregulation of IRF3 activation. In vivo, the use of genetically deficient mice revealed that Th17 inflammatory responses are heightened following H. pylori infection within the context of Sting deficiency in conjunction with increased expression of a known host immune regulator, Trim30a. This novel mechanism of immune suppression by H. pylori is likely a critical component of a finely tuned rheostat that not only regulates the initial innate immune response, but also drives chronic gastric inflammation and injury.
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spelling pubmed-93413742022-08-02 Helicobacter pylori actively suppresses innate immune nucleic acid receptors Dooyema, Samuel D.R. Noto, Jennifer M. Wroblewski, Lydia E. Piazuelo, M. Blanca Krishna, Uma Suarez, Giovanni Romero-Gallo, Judith Delgado, Alberto G. Peek, Richard M. Gut Microbes Research Paper Chronic mucosal pathogens have evolved multiple strategies to manipulate the host immune response; consequently, microbes contribute to the development of >2 million cases of cancer/year. Gastric adenocarcinoma is the fourth leading cause of cancer-related death and Helicobacter pylori confers the highest risk for this disease. Gastric innate immune effectors can either eliminate bacteria or mobilize adaptive immune responses including Toll-like receptors (TLRs), and cytosolic DNA sensor/adaptor proteins (e.g., stimulator of interferon genes, STING). The H. pylori strain-specific cag type IV secretion system (T4SS) augments gastric cancer risk and translocates DNA into epithelial cells where it activates the microbial DNA sensor TLR9 and suppresses injury in vivo; however, the ability of H. pylori to suppress additional nucleic acid PRRs within the context of chronic gastric inflammation and injury remains undefined. In this study, in vitro and ex vivo experiments identified a novel mechanism through which H. pylori actively suppresses STING and RIG-I signaling via downregulation of IRF3 activation. In vivo, the use of genetically deficient mice revealed that Th17 inflammatory responses are heightened following H. pylori infection within the context of Sting deficiency in conjunction with increased expression of a known host immune regulator, Trim30a. This novel mechanism of immune suppression by H. pylori is likely a critical component of a finely tuned rheostat that not only regulates the initial innate immune response, but also drives chronic gastric inflammation and injury. Taylor & Francis 2022-07-29 /pmc/articles/PMC9341374/ /pubmed/35905376 http://dx.doi.org/10.1080/19490976.2022.2105102 Text en © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Dooyema, Samuel D.R.
Noto, Jennifer M.
Wroblewski, Lydia E.
Piazuelo, M. Blanca
Krishna, Uma
Suarez, Giovanni
Romero-Gallo, Judith
Delgado, Alberto G.
Peek, Richard M.
Helicobacter pylori actively suppresses innate immune nucleic acid receptors
title Helicobacter pylori actively suppresses innate immune nucleic acid receptors
title_full Helicobacter pylori actively suppresses innate immune nucleic acid receptors
title_fullStr Helicobacter pylori actively suppresses innate immune nucleic acid receptors
title_full_unstemmed Helicobacter pylori actively suppresses innate immune nucleic acid receptors
title_short Helicobacter pylori actively suppresses innate immune nucleic acid receptors
title_sort helicobacter pylori actively suppresses innate immune nucleic acid receptors
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9341374/
https://www.ncbi.nlm.nih.gov/pubmed/35905376
http://dx.doi.org/10.1080/19490976.2022.2105102
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