Honke Nadine, Shaabani Namir, Hardt Cornelia, Krings Caroline, Häussinger Dieter, Lang Philipp A, Lang Karl S, Keitel Verena
Cell Physiol Biochem. 2017;41(1):323-338. doi: 10.1159/000456168. Epub 2017 Jan 25.
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.
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.
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.
We found that FXR contributes to IFN-I production in hepatocytes and balances BA levels to inhibit their toxic effects on monocytes.
胆汁酸（BAs）是在肝脏中合成的类固醇分子。除了作为表面活性剂在胃肠道中溶解脂质和促进脂质吸收方面发挥重要作用外，它们还作为炎症原发挥作用。胆汁酸及其受体法尼醇X受体（FXR）在病毒感染期间的作用尚未得到详细研究。
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。研究了FXR在诱导I型干扰素和单核细胞增殖中的重要性，并在不同时间点分析了病毒滴度和T细胞耗竭情况。
本研究表明，受控水平的胆汁酸激活肝细胞中的FXR，作为响应，FXR上调I型干扰素的产生。反过来，FXR将胆汁酸维持在平衡范围内以抑制其毒性作用。FXR的缺失导致胆汁酸水平升高，这会抑制单核细胞的增殖并导致病毒清除缺陷，从而导致T细胞耗竭。
我们发现FXR有助于肝细胞中I型干扰素的产生，并平衡胆汁酸水平以抑制其对单核细胞的毒性作用。
