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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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Autores principales: Kaewduangduen, Warerat, Visitchanakun, Peerapat, Saisorn, Wilasinee, Phawadee, Ariya, Manonitnantawat, Charintorn, Chutimaskul, Chirapas, Susantitaphong, Paweena, Ritprajak, Patcharee, Somboonna, Naraporn, Cheibchalard, Thanya, Wannigama, Dhammika Leshan, Kueanjinda, Patipark, Leelahavanichkul, Asada
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836862/
https://www.ncbi.nlm.nih.gov/pubmed/35163830
http://dx.doi.org/10.3390/ijms23031907
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author Kaewduangduen, Warerat
Visitchanakun, Peerapat
Saisorn, Wilasinee
Phawadee, Ariya
Manonitnantawat, Charintorn
Chutimaskul, Chirapas
Susantitaphong, Paweena
Ritprajak, Patcharee
Somboonna, Naraporn
Cheibchalard, Thanya
Wannigama, Dhammika Leshan
Kueanjinda, Patipark
Leelahavanichkul, Asada
author_facet Kaewduangduen, Warerat
Visitchanakun, Peerapat
Saisorn, Wilasinee
Phawadee, Ariya
Manonitnantawat, Charintorn
Chutimaskul, Chirapas
Susantitaphong, Paweena
Ritprajak, Patcharee
Somboonna, Naraporn
Cheibchalard, Thanya
Wannigama, Dhammika Leshan
Kueanjinda, Patipark
Leelahavanichkul, Asada
author_sort Kaewduangduen, Warerat
collection PubMed
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 (NFκB, iNOS, and IL-1β), 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.
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spelling pubmed-88368622022-02-12 Blood Bacteria-Free DNA in Septic Mice Enhances LPS-Induced Inflammation in Mice through Macrophage Response Kaewduangduen, Warerat Visitchanakun, Peerapat Saisorn, Wilasinee Phawadee, Ariya Manonitnantawat, Charintorn Chutimaskul, Chirapas Susantitaphong, Paweena Ritprajak, Patcharee Somboonna, Naraporn Cheibchalard, Thanya Wannigama, Dhammika Leshan Kueanjinda, Patipark Leelahavanichkul, Asada Int J Mol Sci Article 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 (NFκB, iNOS, and IL-1β), 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. MDPI 2022-02-08 /pmc/articles/PMC8836862/ /pubmed/35163830 http://dx.doi.org/10.3390/ijms23031907 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kaewduangduen, Warerat
Visitchanakun, Peerapat
Saisorn, Wilasinee
Phawadee, Ariya
Manonitnantawat, Charintorn
Chutimaskul, Chirapas
Susantitaphong, Paweena
Ritprajak, Patcharee
Somboonna, Naraporn
Cheibchalard, Thanya
Wannigama, Dhammika Leshan
Kueanjinda, Patipark
Leelahavanichkul, Asada
Blood Bacteria-Free DNA in Septic Mice Enhances LPS-Induced Inflammation in Mice through Macrophage Response
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836862/
https://www.ncbi.nlm.nih.gov/pubmed/35163830
http://dx.doi.org/10.3390/ijms23031907
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