Blood Bacteria-Free DNA in Septic Mice Enhances LPS-Induced Inflammation in Mice through Macrophage Response
Although bacteria-free DNA in blood during systemic infection is mainly derived from bacterial death, translocation of the DNA from the gut into the blood circulation (gut translocation) is also possible. Hence, several mouse models with experiments on macrophages were conducted to explore the sourc...
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| Format: | Article |
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/3/1907 |
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| author | Warerat Kaewduangduen Peerapat Visitchanakun Wilasinee Saisorn Ariya Phawadee Charintorn Manonitnantawat Chirapas Chutimaskul Paweena Susantitaphong Patcharee Ritprajak Naraporn Somboonna Thanya Cheibchalard Dhammika Leshan Wannigama Patipark Kueanjinda Asada Leelahavanichkul |
| author_facet | Warerat Kaewduangduen Peerapat Visitchanakun Wilasinee Saisorn Ariya Phawadee Charintorn Manonitnantawat Chirapas Chutimaskul Paweena Susantitaphong Patcharee Ritprajak Naraporn Somboonna Thanya Cheibchalard Dhammika Leshan Wannigama Patipark Kueanjinda Asada Leelahavanichkul |
| author_sort | Warerat Kaewduangduen |
| collection | DOAJ |
| description | Although bacteria-free DNA in blood during systemic infection is mainly derived from bacterial death, translocation of the DNA from the gut into the blood circulation (gut translocation) is also possible. Hence, several mouse models with experiments on macrophages were conducted to explore the sources, influences, and impacts of bacteria-free DNA in sepsis. First, bacteria-free DNA and bacteriome in blood were demonstrated in cecal ligation and puncture (CLP) sepsis mice. Second, administration of bacterial lysate (a source of bacterial DNA) in dextran sulfate solution (DSS)-induced mucositis mice elevated blood bacteria-free DNA without bacteremia supported gut translocation of free DNA. The absence of blood bacteria-free DNA in DSS mice without bacterial lysate implies an impact of the abundance of bacterial DNA in intestinal contents on the translocation of free DNA. Third, higher serum cytokines in mice after injection of combined bacterial DNA with lipopolysaccharide (LPS), when compared to LPS injection alone, supported an influence of blood bacteria-free DNA on systemic inflammation. The synergistic effects of free DNA and LPS on macrophage pro-inflammatory responses, as indicated by supernatant cytokines (TNF-α, IL-6, and IL-10), pro-inflammatory genes (<i>NFκB</i>, <i>iNOS</i>, and <i>IL-1β</i>), and profound energy alteration (enhanced glycolysis with reduced mitochondrial functions), which was neutralized by TLR-9 inhibition (chloroquine), were demonstrated. In conclusion, the presence of bacteria-free DNA in sepsis mice is partly due to gut translocation of bacteria-free DNA into the systemic circulation, which would enhance sepsis severity. Inhibition of the responses against bacterial DNA by TLR-9 inhibition could attenuate LPS-DNA synergy in macrophages and might help improve sepsis hyper-inflammation in some situations. |
| first_indexed | 2024-03-09T23:42:55Z |
| format | Article |
| id | doaj.art-73663be0695744cd85c593ece53c47ac |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:42:55Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-73663be0695744cd85c593ece53c47ac2023-11-23T16:48:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01233190710.3390/ijms23031907Blood Bacteria-Free DNA in Septic Mice Enhances LPS-Induced Inflammation in Mice through Macrophage ResponseWarerat Kaewduangduen0Peerapat Visitchanakun1Wilasinee Saisorn2Ariya Phawadee3Charintorn Manonitnantawat4Chirapas Chutimaskul5Paweena Susantitaphong6Patcharee Ritprajak7Naraporn Somboonna8Thanya Cheibchalard9Dhammika Leshan Wannigama10Patipark Kueanjinda11Asada Leelahavanichkul12Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandNephrology Unit, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandResearch Unit in Integrative Immuno-Microbial Biochemistry and Bioresponsive Nanomaterials, Department of Microbiology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, ThailandMicrobiome Research Unit for Probiotics in Food and Cosmetics, Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok 10330, ThailandProgram in Biotechnology, Faculty of Science, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, ThailandAlthough bacteria-free DNA in blood during systemic infection is mainly derived from bacterial death, translocation of the DNA from the gut into the blood circulation (gut translocation) is also possible. Hence, several mouse models with experiments on macrophages were conducted to explore the sources, influences, and impacts of bacteria-free DNA in sepsis. First, bacteria-free DNA and bacteriome in blood were demonstrated in cecal ligation and puncture (CLP) sepsis mice. Second, administration of bacterial lysate (a source of bacterial DNA) in dextran sulfate solution (DSS)-induced mucositis mice elevated blood bacteria-free DNA without bacteremia supported gut translocation of free DNA. The absence of blood bacteria-free DNA in DSS mice without bacterial lysate implies an impact of the abundance of bacterial DNA in intestinal contents on the translocation of free DNA. Third, higher serum cytokines in mice after injection of combined bacterial DNA with lipopolysaccharide (LPS), when compared to LPS injection alone, supported an influence of blood bacteria-free DNA on systemic inflammation. The synergistic effects of free DNA and LPS on macrophage pro-inflammatory responses, as indicated by supernatant cytokines (TNF-α, IL-6, and IL-10), pro-inflammatory genes (<i>NFκB</i>, <i>iNOS</i>, and <i>IL-1β</i>), and profound energy alteration (enhanced glycolysis with reduced mitochondrial functions), which was neutralized by TLR-9 inhibition (chloroquine), were demonstrated. In conclusion, the presence of bacteria-free DNA in sepsis mice is partly due to gut translocation of bacteria-free DNA into the systemic circulation, which would enhance sepsis severity. Inhibition of the responses against bacterial DNA by TLR-9 inhibition could attenuate LPS-DNA synergy in macrophages and might help improve sepsis hyper-inflammation in some situations.https://www.mdpi.com/1422-0067/23/3/1907sepsisbacterial DNALPSblood microbiome analysiscecal ligation and puncture |
| spellingShingle | Warerat Kaewduangduen Peerapat Visitchanakun Wilasinee Saisorn Ariya Phawadee Charintorn Manonitnantawat Chirapas Chutimaskul Paweena Susantitaphong Patcharee Ritprajak Naraporn Somboonna Thanya Cheibchalard Dhammika Leshan Wannigama Patipark Kueanjinda Asada Leelahavanichkul Blood Bacteria-Free DNA in Septic Mice Enhances LPS-Induced Inflammation in Mice through Macrophage Response International Journal of Molecular Sciences sepsis bacterial DNA LPS blood microbiome analysis cecal ligation and puncture |
| title | Blood Bacteria-Free DNA in Septic Mice Enhances LPS-Induced Inflammation in Mice through Macrophage Response |
| title_full | Blood Bacteria-Free DNA in Septic Mice Enhances LPS-Induced Inflammation in Mice through Macrophage Response |
| title_fullStr | Blood Bacteria-Free DNA in Septic Mice Enhances LPS-Induced Inflammation in Mice through Macrophage Response |
| title_full_unstemmed | Blood Bacteria-Free DNA in Septic Mice Enhances LPS-Induced Inflammation in Mice through Macrophage Response |
| title_short | Blood Bacteria-Free DNA in Septic Mice Enhances LPS-Induced Inflammation in Mice through Macrophage Response |
| title_sort | blood bacteria free dna in septic mice enhances lps induced inflammation in mice through macrophage response |
| topic | sepsis bacterial DNA LPS blood microbiome analysis cecal ligation and puncture |
| url | https://www.mdpi.com/1422-0067/23/3/1907 |
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