Farnesoid X Receptor in Mice Prevents Severe Liver Immunopathology During Lymphocytic Choriomeningitis Virus Infection
Farnesoid X Receptor in Mice Prevents Severe Liver Immunopathology During Lymphocytic Choriomeningitis Virus Infection
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DOI：
10.1159/000456168
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Lang, Karl S.
中科院分区：
文献类型：
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作者：
Honke, Nadine;Shaabani, Namir;Lang, Karl S.
背景：胆汁酸（BA）是在肝脏中合成的类固醇分子。除了作为表面活性剂在增溶脂质和促进胃肠道中脂质吸收方面的重要作用外，它们还充当炎性因子。BA及其受体法尼醇X受体（FXR）在病毒感染过程中的作用尚未详细研究。研究方法：通过使用FXR缺陷小鼠，我们研究了胆汁酸受体FXR在淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染过程中的作用。研究FXR在诱导IFN-1和单核细胞增殖中的重要性，并在不同时间点分析病毒滴度和T细胞耗竭。结果如下：这项研究表明，控制水平的BA激活肝细胞中的FXR，FXR作为响应上调I型干扰素的产生。反过来，FXR将BA维持在平衡范围内，以抑制其毒性作用。FXR的缺乏导致高水平的BA，从而抑制单核细胞的增殖并导致病毒清除缺陷，从而导致T细胞衰竭。结论：FXR可促进肝细胞IFN-Ⅰ的产生，平衡BA水平，抑制其对单核细胞的毒性作用。(C)2017作者（s）由S. Karger AG，巴塞尔
Background: Bile acids (BAs) are steroid molecules that are synthesized in the liver. In addition to their important role as a surfactant in solubilizing lipids and promoting the absorption of lipids in the gastrointestinal tract, they act as inflammagens. The role of BAs and their receptor farnesoid X receptor (FXR) during viral infection has not been studied in detail. Methods: By using FXR-deficient mice, we investigated the role of bile acid receptor FXR during infection with lymphocytic choriomeningitis virus (LCMV). The importance of FXR in inducing IFN-I and monocytes proliferation were investigated and viral titers and T cell exhaustion were analyzed at different time points. Results: This study shows that controlled levels of BAs activate FXR in hepatocytes and FXR in response upregulates the production of type I interferon. In turn, FXR maintains BAs within a balanced range to inhibit their toxic effects. The absence of FXR results in high levels of BAs, which inhibit the proliferation of monocytes and result in a defect in viral elimination, consequently leading to T cell exhaustion. Conclusion: We found that FXR contributes to IFN-I production in hepatocytes and balances BA levels to inhibit their toxic effects on monocytes. (C) 2017 The Author( s) Published by S. Karger AG, Basel