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Temporal changes of NF-κB signaling pathway genes in bacterial stimulated whole blood- a host mechanism associated with sepsis.
Microbial Pathogenesis ( IF 3.8 ) Pub Date : 2020-07-29 , DOI: 10.1016/j.micpath.2020.104415
Athira Anirudhan 1 , Prabu Paramasivam 2 , Ram Murugesan 1 , Shiek S S J Ahmed 1
Affiliation  

Bacterial sepsis affects both neonates and adults worldwide. There is no specific anti-sepsis treatment. Disease management mainly depends on early diagnosis. The gold standard blood culturing method is routinely practiced; it requires 24–48 h for confirmation. Understanding the disease mechanism may help in the early detection of sepsis. We studied the temporal change in NF-kB pathway genes in adult whole blood upon bacterial stimulations across time intervals (2–6 h). Four experimental conditions were investigated (1: Gram-positive, 2: Gram-negative, 3: Gram-positive + Gram-negative stimulated and compared with 4: un-stimulated group) to show host selection of canonical or non-canonical pathway against invading pathogens. Gene expression analysis showed significant variations (p < 0.5) in TLR2, TLR4, TRAF6, NIK, RelA, and RelB upon bacterial stimulants. Further, the correlation analysis showed the coherent behaviour of genes in selecting the canonical or non-canonical pathway. TLR2 sensed by gram-positive bacteria that immediately activates the canonical pathway through RelA, whereas other bacterial stimulants activate the non-canonical pathway via TLR4, NIK, and RelB. In addition, the inflammatory markers showed a significant increase in response to bacterial stimulants, suggesting the immediate activation of innate immunity. Overall, our results show the bacterial specific and time-dependent activation of the NF-kB pathway, which through a light towards the early detection of bacterial sepsis.



中文翻译:

细菌刺激的全血中NF-κB信号通路基因的时间变化-一种与败血症相关的宿主机制。

细菌性败血症影响全世界的新生儿和成年人。没有特异性的防腐治疗。疾病管理主要取决于早期诊断。金标准的血液培养方法是常规实施的。确认需要24–48小时。了解疾病的机制可能有助于败血症的早期发现。我们研究了在整个时间间隔(2–6小时)中细菌刺激后成人全血中NF-kB通路基因的时间变化。研究了四个实验条件(1:革兰氏阳性,2:革兰氏阴性,3:革兰氏阳性+革兰氏阴性刺激,并与4:未刺激组进行比较),以显示针对宿主的经典或非经典途径的宿主选择入侵病原体。基因表达分析显示出显着差异(p 细菌刺激后在TLR2,TLR4,TRAF6,NIK,RelA和RelB中的<0.5)。此外,相关性分析显示了基因在选择经典或非经典途径中的相干行为。革兰氏阳性细菌检测到的TLR2立即激活通过RelA的经典途径,而其他细菌刺激剂通过TLR4,NIK和RelB激活非经典途径。另外,炎性标记物显示出对细菌刺激物的应答显着增加,表明先天免疫的立即激活。总的来说,我们的结果显示了NF-kB途径的细菌特异性和时间依赖性激活,这是通过对细菌性败血症的早期检测来实现的。

更新日期:2020-07-29
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