Involvement of Commensal Bacteria may Lead to Dysregulated Inflammatory and Autoimmune Responses in a Mouse Model for Chronic Nonsuppurative Destructive Cholangitis
Involvement of Commensal Bacteria may Lead to Dysregulated Inflammatory and Autoimmune Responses in a Mouse Model for Chronic Nonsuppurative Destructive Cholangitis
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DOI：
10.1007/s10875-012-9712-1
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发表时间：
2012-10-01
影响因子：
9.1
通讯作者：
Yagi, Junji
中科院分区：
文献类型：
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作者：
Haruta, Ikuko;Kikuchi, Ken;Yagi, Junji
我们先前报道了一种小鼠模型的原发性胆汁性肝硬化（PBC）样慢性非化脓性破坏性胆管炎（CNSDC），其中频繁注射中间链球菌诱导CNSDC和自身抗体的产生。本研究通过检查1）在从模型小鼠向未处理小鼠转移淋巴细胞后PBMC样CNSDC的再现、2）自噬的参与和3）品系差异的影响来验证该模型。中间肌每周一次，持续8周，然后处死以获得样品。从S.将中间体接种的小鼠转移到RAG 2（-/-）小鼠，在S.中间体接种的C57 BL/6小鼠，类似于我们先前使用BALB/c小鼠的报告的结果。通过转移来自S.接种中间体的C57 BL/6小鼠。在RAG 2（-/-）小鼠的炎性细胞中，CD 3阳性细胞占主导地位。组织学上，在肝胆管周围浸润细胞的胞浆中发现自噬体样结构。中间体接种C57 BL/6和BALB/c小鼠。In S.感染C3 H/HeJ小鼠，汇管区的炎症反应比肝实质的炎症反应轻，细菌成分和随后上调的先天性和获得性免疫反应，伴随自噬，可能通过自身免疫机制触发CNSDC。在细菌诱导的PBC-like CNSDC的产生过程中，菌株差异可能影响对S.中间接种在肝脏中。
We previously reported a mouse model of primary biliary cirrhosis (PBC)-like chronic nonsuppurative destructive cholangitis (CNSDC), in which frequent injections of Streptococcus intermedius induced CNSDC and autoantibody production. The present study was performed to verify the model by examining 1) the reappearance of the PBC-like CNSDC after lymphocyte transfer from model to na < ve mice, 2) the involvement of autophagy, and 3) the influence of the strain difference.Mice were inoculated with S. intermedius weekly for 8 weeks, then sacrificed to obtain samples. Spleen cells obtained from S. intermedius-inoculated mice were transferred to RAG2(-/-) mice.CNSDC and elevated serum level of anti-gp210 titers were observed in S. intermedius-inoculated C57BL/6 mice, similar to the results of our previous report using BALB/c mice. Portal inflammation was induced in the livers of RAG2(-/-) mice by the transfer of spleen cells from S. intermedius-inoculated C57BL/6 mice. Among the inflammatory cells in the RAG2(-/-) mice, CD3-positive cells were predominant. Autophagosome-like structures were detected histologically, in the cytoplasm of infiltrated cells around the bile ducts in the livers of S. intermedius-inoculated both C57BL/6 and BALB/c mice. In S. intermedius-inoculated C3H/HeJ mice, inflammation in the portal area was less extensive than that in the hepatic parenchyma.Bacterial component(s) and sequentially upregulated innate and acquired immune responses, accompanied by autophagy, might trigger CNSDC, via autoimmune mechanisms. Throughout the generation of bacteria-triggered PBC-like CNSDC, strain difference may influence the response to S. intermedius-inoculation in the liver.