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Sensing Bacterial-Induced DNA Damaging Effects via Natural Killer Group 2 Member D Immune Receptor: From Dysbiosis to Autoimmunity and Carcinogenesis
The human genome is constantly exposed to exogenous and endogenous DNA damaging factors that frequently cause DNA damages. Unless repaired, damaged DNA can result in deleterious mutations capable of causing malignant transformation. Accordingly, cells have developed an advanced and effective surveil...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788971/ https://www.ncbi.nlm.nih.gov/pubmed/29422899 http://dx.doi.org/10.3389/fimmu.2018.00052 |
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author | Espinoza, J. Luis Minami, Mika |
author_facet | Espinoza, J. Luis Minami, Mika |
author_sort | Espinoza, J. Luis |
collection | PubMed |
description | The human genome is constantly exposed to exogenous and endogenous DNA damaging factors that frequently cause DNA damages. Unless repaired, damaged DNA can result in deleterious mutations capable of causing malignant transformation. Accordingly, cells have developed an advanced and effective surveillance system, the DNA damage response (DDR) pathway, which maintains genetic integrity. In addition to well-defined outcomes, such as cell cycle arrest, apoptosis, and senescence, another consequence of DDR activation is the induction of natural killer group 2 member D ligands (NKG2D-Ls) on the surface of stressed cells. Consequently, NKG2D-Ls-expressing cells are recognized and eliminated by NKG2D receptor-expressing immune cells, including NK cells, and various subsets of T-cells. Recent pieces of evidence indicate that commensal microbial imbalance (known as dysbiosis) can trigger DDR activation in host cells, which may result in sustained inflammatory responses. Therefore, dysbiosis can be seen as an important source of DNA damage agents that may be partially responsible for the overexpression of NKG2D-Ls on intestinal epithelial cells that is frequently observed in patients with inflammatory bowel disease and other disorders associated with altered human microbiota, including the development of colorectal cancer. In this article, we discuss recent evidence that appears to link an altered human microbiota with autoimmunity and carcinogenesis via the activation of DDR signals and the induction of NKG2D-Ls in stressed cells. |
format | Online Article Text |
id | pubmed-5788971 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57889712018-02-08 Sensing Bacterial-Induced DNA Damaging Effects via Natural Killer Group 2 Member D Immune Receptor: From Dysbiosis to Autoimmunity and Carcinogenesis Espinoza, J. Luis Minami, Mika Front Immunol Immunology The human genome is constantly exposed to exogenous and endogenous DNA damaging factors that frequently cause DNA damages. Unless repaired, damaged DNA can result in deleterious mutations capable of causing malignant transformation. Accordingly, cells have developed an advanced and effective surveillance system, the DNA damage response (DDR) pathway, which maintains genetic integrity. In addition to well-defined outcomes, such as cell cycle arrest, apoptosis, and senescence, another consequence of DDR activation is the induction of natural killer group 2 member D ligands (NKG2D-Ls) on the surface of stressed cells. Consequently, NKG2D-Ls-expressing cells are recognized and eliminated by NKG2D receptor-expressing immune cells, including NK cells, and various subsets of T-cells. Recent pieces of evidence indicate that commensal microbial imbalance (known as dysbiosis) can trigger DDR activation in host cells, which may result in sustained inflammatory responses. Therefore, dysbiosis can be seen as an important source of DNA damage agents that may be partially responsible for the overexpression of NKG2D-Ls on intestinal epithelial cells that is frequently observed in patients with inflammatory bowel disease and other disorders associated with altered human microbiota, including the development of colorectal cancer. In this article, we discuss recent evidence that appears to link an altered human microbiota with autoimmunity and carcinogenesis via the activation of DDR signals and the induction of NKG2D-Ls in stressed cells. Frontiers Media S.A. 2018-01-25 /pmc/articles/PMC5788971/ /pubmed/29422899 http://dx.doi.org/10.3389/fimmu.2018.00052 Text en Copyright © 2018 Espinoza and Minami. http://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) or licensor 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 Espinoza, J. Luis Minami, Mika Sensing Bacterial-Induced DNA Damaging Effects via Natural Killer Group 2 Member D Immune Receptor: From Dysbiosis to Autoimmunity and Carcinogenesis |
title | Sensing Bacterial-Induced DNA Damaging Effects via Natural Killer Group 2 Member D Immune Receptor: From Dysbiosis to Autoimmunity and Carcinogenesis |
title_full | Sensing Bacterial-Induced DNA Damaging Effects via Natural Killer Group 2 Member D Immune Receptor: From Dysbiosis to Autoimmunity and Carcinogenesis |
title_fullStr | Sensing Bacterial-Induced DNA Damaging Effects via Natural Killer Group 2 Member D Immune Receptor: From Dysbiosis to Autoimmunity and Carcinogenesis |
title_full_unstemmed | Sensing Bacterial-Induced DNA Damaging Effects via Natural Killer Group 2 Member D Immune Receptor: From Dysbiosis to Autoimmunity and Carcinogenesis |
title_short | Sensing Bacterial-Induced DNA Damaging Effects via Natural Killer Group 2 Member D Immune Receptor: From Dysbiosis to Autoimmunity and Carcinogenesis |
title_sort | sensing bacterial-induced dna damaging effects via natural killer group 2 member d immune receptor: from dysbiosis to autoimmunity and carcinogenesis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5788971/ https://www.ncbi.nlm.nih.gov/pubmed/29422899 http://dx.doi.org/10.3389/fimmu.2018.00052 |
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