Blood Bacteria-Free DNA in Septic Mice Enhances LPS-Induced Inflammation in Mice through Macrophage Response.
Blood Bacteria-Free DNA in Septic Mice Enhances LPS-Induced Inflammation in Mice through Macrophage Response.
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DOI：
10.3390/ijms23031907
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发表时间：
2022-02-08
影响因子：
5.6
通讯作者：
Leelahavanichkul A
中科院分区：
文献类型：
--
作者：
Kaewduangduen W;Visitchanakun P;Saisorn W;Phawadee A;Manonitnantawat C;Chutimaskul C;Susantitaphong P;Ritprajak P;Somboonna N;Cheibchalard T;Wannigama DL;Kueanjinda P;Leelahavanichkul A
虽然全身感染期间血液中的无菌DNA主要来自细菌死亡，但DNA从肠道易位到血液循环中（肠道易位）也是可能的。因此，进行了几种具有巨噬细胞实验的小鼠模型，以探索脓毒症中无菌DNA的来源、影响和作用。首先，在盲肠结扎穿孔（CLP）脓毒症小鼠中证实了血液中的无菌DNA和细菌组。其次，在硫酸葡聚糖溶液（DSS）诱导的粘膜炎小鼠中施用细菌裂解物（细菌DNA的来源）升高血液无菌DNA，而没有菌血症支持游离DNA的肠道易位。在没有细菌裂解物的DSS小鼠中血液无细菌DNA的缺乏意味着肠内容物中细菌DNA的丰度对游离DNA的易位的影响。第三，与单独注射LPS相比，注射细菌DNA与脂多糖（LPS）组合后小鼠中较高的血清细胞因子支持血液无菌DNA对全身炎症的影响。如上清液细胞因子（TNF-α、IL-6和IL-10）、促炎基因（NFκB、iNOS和IL-1β）所示，游离DNA和LPS对巨噬细胞促炎反应具有协同作用。证实了能量改变（糖酵解增强，线粒体功能降低），并被TLR-9抑制剂（氯喹）所中和。总之，脓毒症小鼠中存在无菌DNA部分是由于无菌DNA的肠道易位进入体循环，这将增加脓毒症的严重程度。通过TLR-9抑制对细菌DNA的反应的抑制可以减弱巨噬细胞中的LPS-DNA协同作用，并且在某些情况下可能有助于改善脓毒症过度炎症。
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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DOI：
10.1016/j.surge.2012.03.003
发表时间：
2012-12
影响因子：
2.5
作者：
Deitch, Edwin A.
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影响因子：
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通讯作者：
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影响因子：
4.6
作者：
Gargari G;Mantegazza G;Taverniti V;Del Bo' C;Bernardi S;Andres-Lacueva C;González-Domínguez R;Kroon PA;Winterbone MS;Cherubini A;Riso P;Guglielmetti S
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