Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors

The basic function of the immune system is the protection of the host against infections, along with the preservation of the individual antigenic identity. The process of self-tolerance covers the discrimination between self and foreign antigens, including proteins, nucleic acids, and larger molecul...

Full description

Bibliographic Details
Main Authors: Györgyi Műzes, Bettina Bohusné Barta, Orsolya Szabó, Vanessza Horgas, Ferenc Sipos
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/11/2853
_version_ 1827647164856139776
author Györgyi Műzes
Bettina Bohusné Barta
Orsolya Szabó
Vanessza Horgas
Ferenc Sipos
author_facet Györgyi Műzes
Bettina Bohusné Barta
Orsolya Szabó
Vanessza Horgas
Ferenc Sipos
author_sort Györgyi Műzes
collection DOAJ
description The basic function of the immune system is the protection of the host against infections, along with the preservation of the individual antigenic identity. The process of self-tolerance covers the discrimination between self and foreign antigens, including proteins, nucleic acids, and larger molecules. Consequently, a broken immunological self-tolerance results in the development of autoimmune or autoinflammatory disorders. Immunocompetent cells express pattern-recognition receptors on their cell membrane and cytoplasm. The majority of endogenous DNA is located intracellularly within nuclei and mitochondria. However, extracellular, cell-free DNA (cfDNA) can also be detected in a variety of diseases, such as autoimmune disorders and malignancies, which has sparked interest in using cfDNA as a possible biomarker. In recent years, the widespread use of liquid biopsies and the increasing demand for screening, as well as monitoring disease activity and therapy response, have enabled the revival of cfDNA research. The majority of studies have mainly focused on the function of cfDNA as a biomarker. However, research regarding the immunological consequences of cfDNA, such as its potential immunomodulatory or therapeutic benefits, is still in its infancy. This article discusses the involvement of various DNA-sensing receptors (e.g., absent in melanoma-2; Toll-like receptor 9; cyclic GMP–AMP synthase/activator of interferon genes) in identifying host cfDNA as a potent danger-associated molecular pattern. Furthermore, we aim to summarize the results of the experimental studies that we recently performed and highlight the immunomodulatory capacity of cfDNA, and thus, the potential for possible therapeutic consideration.
first_indexed 2024-03-09T19:15:23Z
format Article
id doaj.art-a4b0d3c8aab2435ca5e2b4deb41c3eb7
institution Directory Open Access Journal
issn 2227-9059
language English
last_indexed 2024-03-09T19:15:23Z
publishDate 2022-11-01
publisher MDPI AG
record_format Article
series Biomedicines
spelling doaj.art-a4b0d3c8aab2435ca5e2b4deb41c3eb72023-11-24T03:51:45ZengMDPI AGBiomedicines2227-90592022-11-011011285310.3390/biomedicines10112853Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and TumorsGyörgyi Műzes0Bettina Bohusné Barta1Orsolya Szabó2Vanessza Horgas3Ferenc Sipos4Department of Internal Medicine and Hematology, Semmelweis University, Szentkirályi Street 46, 1088 Budapest, HungaryDepartment of Internal Medicine and Hematology, Semmelweis University, Szentkirályi Street 46, 1088 Budapest, HungaryDepartment of Internal Medicine and Hematology, Semmelweis University, Szentkirályi Street 46, 1088 Budapest, HungaryDepartment of Internal Medicine and Hematology, Semmelweis University, Szentkirályi Street 46, 1088 Budapest, HungaryDepartment of Internal Medicine and Hematology, Semmelweis University, Szentkirályi Street 46, 1088 Budapest, HungaryThe basic function of the immune system is the protection of the host against infections, along with the preservation of the individual antigenic identity. The process of self-tolerance covers the discrimination between self and foreign antigens, including proteins, nucleic acids, and larger molecules. Consequently, a broken immunological self-tolerance results in the development of autoimmune or autoinflammatory disorders. Immunocompetent cells express pattern-recognition receptors on their cell membrane and cytoplasm. The majority of endogenous DNA is located intracellularly within nuclei and mitochondria. However, extracellular, cell-free DNA (cfDNA) can also be detected in a variety of diseases, such as autoimmune disorders and malignancies, which has sparked interest in using cfDNA as a possible biomarker. In recent years, the widespread use of liquid biopsies and the increasing demand for screening, as well as monitoring disease activity and therapy response, have enabled the revival of cfDNA research. The majority of studies have mainly focused on the function of cfDNA as a biomarker. However, research regarding the immunological consequences of cfDNA, such as its potential immunomodulatory or therapeutic benefits, is still in its infancy. This article discusses the involvement of various DNA-sensing receptors (e.g., absent in melanoma-2; Toll-like receptor 9; cyclic GMP–AMP synthase/activator of interferon genes) in identifying host cfDNA as a potent danger-associated molecular pattern. Furthermore, we aim to summarize the results of the experimental studies that we recently performed and highlight the immunomodulatory capacity of cfDNA, and thus, the potential for possible therapeutic consideration.https://www.mdpi.com/2227-9059/10/11/2853cell-free DNACpG oligonucleotidesinflammationautoimmunitytumorabsent in melanoma-2
spellingShingle Györgyi Műzes
Bettina Bohusné Barta
Orsolya Szabó
Vanessza Horgas
Ferenc Sipos
Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors
Biomedicines
cell-free DNA
CpG oligonucleotides
inflammation
autoimmunity
tumor
absent in melanoma-2
title Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors
title_full Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors
title_fullStr Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors
title_full_unstemmed Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors
title_short Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors
title_sort cell free dna in the pathogenesis and therapy of non infectious inflammations and tumors
topic cell-free DNA
CpG oligonucleotides
inflammation
autoimmunity
tumor
absent in melanoma-2
url https://www.mdpi.com/2227-9059/10/11/2853
work_keys_str_mv AT gyorgyimuzes cellfreednainthepathogenesisandtherapyofnoninfectiousinflammationsandtumors
AT bettinabohusnebarta cellfreednainthepathogenesisandtherapyofnoninfectiousinflammationsandtumors
AT orsolyaszabo cellfreednainthepathogenesisandtherapyofnoninfectiousinflammationsandtumors
AT vanesszahorgas cellfreednainthepathogenesisandtherapyofnoninfectiousinflammationsandtumors
AT ferencsipos cellfreednainthepathogenesisandtherapyofnoninfectiousinflammationsandtumors