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鉴定乙型肝炎病毒转基因小鼠和慢性乙型肝炎患者肝脏中的促炎型 CD205 巨噬细胞。

Identification of pro-inflammatory CD205 macrophages in livers of hepatitis B virus transgenic mice and patients with chronic hepatitis B.

机构信息

Anhui Provincial Laboratory of Microbiology and Parasitology; Department of Microbiology and Parasitology, Anhui Medical University, Hefei, China.

Intensive Care Unit, Affiliated Provincial Hospital of Anhui Medical University, Hefei, China.

出版信息

Sci Rep. 2017 Apr 24;7:46765. doi: 10.1038/srep46765.

DOI:10.1038/srep46765
PMID:28436459
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5402278/
Abstract

Hepatic macrophages play a central role in disease pathogenesis during hepatitis B virus (HBV) infection. Our previous study found that CD205 macrophages in the liver of hepatitis B surface antigen transgenic (HBs-Tg) mice increased significantly compared with those in wild-type mice, and these increased CD205 macrophages were involved in CpG-oligodeoxynucleotide-induced liver injury in HBs-Tg mice. Here, we analysed the phenotype and function of CD205 macrophages derived from the liver of HBs-Tg mice and patients with chronic hepatitis B (CHB). We found that HBs-Tg mice-derived hepatic macrophages produced larger amounts of pro-inflammatory cytokines, including IL-6, IL-12, TNF-α, and of the anti-inflammatory cytokine IL-10 after stimulation with CpG-oligodeoxynucleotides or commensal bacteria DNA than B6 mice-derived hepatic macrophages. Furthermore, hepatic CD205 macrophages from HBs-Tg mice showed an activated phenotype and expressed higher levels of inflammatory cytokine genes, chemokine genes, and phagocytosis-related genes than hepatic CD205 macrophages. In addition, CD205 macrophages displayed an inflammatory phenotype and were increased in the liver of patients with CHB compared with those in healthy controls. Our data suggest that hepatic CD205 macrophages are a unique pro-inflammatory subset observed during HBV infection. Thus, development of intervention targeting these cells is warranted for immunotherapy of HBV-induced liver diseases.

摘要

肝巨噬细胞在乙型肝炎病毒（HBV）感染期间的疾病发病机制中发挥核心作用。我们之前的研究发现，乙型肝炎表面抗原转基因（HBs-Tg）小鼠肝脏中的 CD205 巨噬细胞与野生型小鼠相比显著增加，这些增加的 CD205 巨噬细胞参与了 HBs-Tg 小鼠中 CpG-寡脱氧核苷酸诱导的肝损伤。在这里，我们分析了 HBs-Tg 小鼠和慢性乙型肝炎（CHB）患者肝脏中 CD205 巨噬细胞的表型和功能。我们发现，HBs-Tg 小鼠来源的肝巨噬细胞在受到 CpG-寡脱氧核苷酸或共生菌 DNA 刺激后，产生了更多的促炎细胞因子，包括 IL-6、IL-12、TNF-α和抗炎细胞因子 IL-10，而 B6 小鼠来源的肝巨噬细胞则没有。此外，HBs-Tg 小鼠的肝 CD205 巨噬细胞表现出激活的表型，并表达更高水平的炎症细胞因子基因、趋化因子基因和吞噬相关基因。此外，与健康对照组相比，CHB 患者肝脏中的 CD205 巨噬细胞表现出炎症表型，并且数量增加。我们的数据表明，肝 CD205 巨噬细胞是在 HBV 感染期间观察到的一种独特的促炎亚群。因此，针对这些细胞的干预措施的发展对于 HBV 诱导的肝脏疾病的免疫治疗是必要的。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0229/5402278/bf1bc2b50427/srep46765-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0229/5402278/ba410a39d4cb/srep46765-f1.jpg
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