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酒精性肝病小鼠感染. 相关基因表达谱、细胞因子和细菌负荷分析

Analysis of Gene Expression Profiles, Cytokines, and Bacterial Loads Relevant to Alcoholic Liver Disease Mice Infected With .

机构信息

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences (AMMS), Beijing, China.

School of Medicine, Jiangsu University, Zhenjiang, China.

出版信息

Front Immunol. 2021 Aug 20;12:695491. doi: 10.3389/fimmu.2021.695491. eCollection 2021.

DOI:10.3389/fimmu.2021.695491
PMID:34489943
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8417779/
Abstract

Patients with liver disease are susceptible to infection with (), but the specific reasons remain elusive. Through RNA-seq, we found that when mice with alcoholic liver disease (ALD) were infected with by gavage, compared with the Pair group, the small intestinal genes affecting intestinal permeability were upregulated; and the number of differentially expressed genes related to immune functions (e.g., such as cell chemotaxis, leukocyte differentiation, and neutrophil degranulation) decreased in the liver, spleen, and blood. Further analysis showed that the number of white blood cells decreased in the Pair group, whereas those in the ALD mice did not change significantly. Interestingly, the blood bacterial load in the ALD mice was about 100 times higher than that of the Pair group. After the ALD mice were infected with , the concentrations of T cell proliferation-promoting cytokines (IL-2, IL-23) decreased. Therefore, unlike the Pair group, ALD mice had weaker immune responses, lower T cell proliferation-promoting cytokines, and higher bacterial loads post-infection, possibly increasing their susceptibility to infection. These new findings we presented here may help to advance the current understanding of the reasons why patients with liver disease are susceptible to infection and provides potential targets for further investigation in the context of treatment options for sepsis in liver disease patient.

摘要

肝病患者易感染(),但具体原因尚不清楚。通过 RNA-seq,我们发现当酒精性肝病(ALD)小鼠经灌胃感染时,与 Pair 组相比,影响肠道通透性的小肠基因上调;并且与免疫功能相关的差异表达基因数量减少在肝脏、脾脏和血液中。进一步分析表明,Pair 组的白细胞数量减少,而 ALD 小鼠的白细胞数量变化不明显。有趣的是,ALD 小鼠的血液细菌负荷约为 Pair 组的 100 倍。感染后,促进 T 细胞增殖的细胞因子(IL-2、IL-23)的浓度降低。因此,与 Pair 组不同,ALD 小鼠感染后免疫反应较弱,促进 T 细胞增殖的细胞因子水平较低,细菌负荷较高,这可能增加了它们感染的易感性。我们在这里提出的这些新发现可能有助于深入了解肝病患者易感染的原因,并为进一步研究肝病患者脓毒症的治疗选择提供潜在目标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e169/8417779/a3bb099186dc/fimmu-12-695491-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e169/8417779/d6f16ee412f5/fimmu-12-695491-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e169/8417779/629cd359dcf0/fimmu-12-695491-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e169/8417779/22a81a2ad4e3/fimmu-12-695491-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e169/8417779/c3e2a6fdc78b/fimmu-12-695491-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e169/8417779/9ebdfcd43ace/fimmu-12-695491-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e169/8417779/53dd6a4c7e50/fimmu-12-695491-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e169/8417779/a3bb099186dc/fimmu-12-695491-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e169/8417779/d6f16ee412f5/fimmu-12-695491-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e169/8417779/629cd359dcf0/fimmu-12-695491-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e169/8417779/22a81a2ad4e3/fimmu-12-695491-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e169/8417779/c3e2a6fdc78b/fimmu-12-695491-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e169/8417779/9ebdfcd43ace/fimmu-12-695491-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e169/8417779/53dd6a4c7e50/fimmu-12-695491-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e169/8417779/a3bb099186dc/fimmu-12-695491-g007.jpg

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