The Central Role and Possible Mechanisms of Bacterial DNAs in Sepsis Development
The pathological roles of bacterial DNA have been documented many decades ago. Bacterial DNAs are different from mammalian DNAs; the latter are heavily methylated. Mammalian cells have sensors such as TLR-9 to sense the DNAs with nonmethylated CpGs and distinguish them from host DNAs with methylated...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/7418342 |
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| author | Zhenxing Cheng Simon T. Abrams James Austin Julien Toh Susan Siyu Wang Zhi Wang Qian Yu Weiping Yu Cheng Hock Toh Guozheng Wang |
| author_facet | Zhenxing Cheng Simon T. Abrams James Austin Julien Toh Susan Siyu Wang Zhi Wang Qian Yu Weiping Yu Cheng Hock Toh Guozheng Wang |
| author_sort | Zhenxing Cheng |
| collection | DOAJ |
| description | The pathological roles of bacterial DNA have been documented many decades ago. Bacterial DNAs are different from mammalian DNAs; the latter are heavily methylated. Mammalian cells have sensors such as TLR-9 to sense the DNAs with nonmethylated CpGs and distinguish them from host DNAs with methylated CpGs. Further investigation has identified many other types of DNA sensors distributed in a variety of cellular compartments. These sensors not only sense foreign DNAs, including bacterial and viral DNAs, but also sense damaged DNAs from the host cells. The major downstream signalling pathways includeTLR-9-MyD88-IKKa-IRF-7/NF-κB pathways to increase IFN/proinflammatory cytokine production, STING-TBK1-IRF3 pathway to increase IFN-beta, and AIM2-ASC-caspas-1 pathway to release IL-1beta. The major outcome is to activate host immune response by inducing cytokine production. In this review, we focus on the roles and potential mechanisms of DNA sensors and downstream pathways in sepsis. Although bacterial DNAs play important roles in sepsis development, bacterial DNAs alone are unable to cause severe disease nor lead to death. Priming animals with bacterial DNAs facilitate other pathological factors, such as LPS and other virulent factors, to induce severe disease and lethality. We also discuss compartmental distribution of DNA sensors and pathological significance as well as the transport of extracellular DNAs into cells. Understanding the roles of DNA sensors and signal pathways will pave the way for novel therapeutic strategies in many diseases, particularly in sepsis. |
| format | Article |
| id | doaj-art-ba19471e345b4e14bc8fc88efb749f9e |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-ba19471e345b4e14bc8fc88efb749f9e2025-02-03T05:44:15ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/74183427418342The Central Role and Possible Mechanisms of Bacterial DNAs in Sepsis DevelopmentZhenxing Cheng0Simon T. Abrams1James Austin2Julien Toh3Susan Siyu Wang4Zhi Wang5Qian Yu6Weiping Yu7Cheng Hock Toh8Guozheng Wang9Department of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, The University of Liverpool, Liverpool, L69 7BE, UKDepartment of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, The University of Liverpool, Liverpool, L69 7BE, UKDepartment of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, The University of Liverpool, Liverpool, L69 7BE, UKWirral University Teaching Hospitals NHS Foundation Trust, Arrowe Park Road, Upton, Wirral CH49 5PE, UKRoyal London Hospital, Whitechapel Rd, Whitechapel, London E1 1FR, UKMedical School, Southeast University, Nanjing 21009, ChinaMedical School, Southeast University, Nanjing 21009, ChinaMedical School, Southeast University, Nanjing 21009, ChinaDepartment of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, The University of Liverpool, Liverpool, L69 7BE, UKDepartment of Clinical Infection, Microbiology and Immunology, Institute of Infection and Global Health, The University of Liverpool, Liverpool, L69 7BE, UKThe pathological roles of bacterial DNA have been documented many decades ago. Bacterial DNAs are different from mammalian DNAs; the latter are heavily methylated. Mammalian cells have sensors such as TLR-9 to sense the DNAs with nonmethylated CpGs and distinguish them from host DNAs with methylated CpGs. Further investigation has identified many other types of DNA sensors distributed in a variety of cellular compartments. These sensors not only sense foreign DNAs, including bacterial and viral DNAs, but also sense damaged DNAs from the host cells. The major downstream signalling pathways includeTLR-9-MyD88-IKKa-IRF-7/NF-κB pathways to increase IFN/proinflammatory cytokine production, STING-TBK1-IRF3 pathway to increase IFN-beta, and AIM2-ASC-caspas-1 pathway to release IL-1beta. The major outcome is to activate host immune response by inducing cytokine production. In this review, we focus on the roles and potential mechanisms of DNA sensors and downstream pathways in sepsis. Although bacterial DNAs play important roles in sepsis development, bacterial DNAs alone are unable to cause severe disease nor lead to death. Priming animals with bacterial DNAs facilitate other pathological factors, such as LPS and other virulent factors, to induce severe disease and lethality. We also discuss compartmental distribution of DNA sensors and pathological significance as well as the transport of extracellular DNAs into cells. Understanding the roles of DNA sensors and signal pathways will pave the way for novel therapeutic strategies in many diseases, particularly in sepsis.http://dx.doi.org/10.1155/2020/7418342 |
| spellingShingle | Zhenxing Cheng Simon T. Abrams James Austin Julien Toh Susan Siyu Wang Zhi Wang Qian Yu Weiping Yu Cheng Hock Toh Guozheng Wang The Central Role and Possible Mechanisms of Bacterial DNAs in Sepsis Development Mediators of Inflammation |
| title | The Central Role and Possible Mechanisms of Bacterial DNAs in Sepsis Development |
| title_full | The Central Role and Possible Mechanisms of Bacterial DNAs in Sepsis Development |
| title_fullStr | The Central Role and Possible Mechanisms of Bacterial DNAs in Sepsis Development |
| title_full_unstemmed | The Central Role and Possible Mechanisms of Bacterial DNAs in Sepsis Development |
| title_short | The Central Role and Possible Mechanisms of Bacterial DNAs in Sepsis Development |
| title_sort | central role and possible mechanisms of bacterial dnas in sepsis development |
| url | http://dx.doi.org/10.1155/2020/7418342 |
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