mBio:厦门大学苏新专教授课题组合作揭示疟疾感染过程中转录因
2017年1月3日，国际微生物学旗舰刊物《mBio》杂志上在线发表了厦门大学生命科学学院苏新专教授与王荣福教授(Houston Methodist Research Institute)课题组的合作研究成果：“FOSL1 Inhibits Type I Interferon Responses to Malaria and Viral Infections by Blocking TBK1 and TRAF3/ TRIF Interactions”，首次揭示了在疟疾感染过程中FOSL1能调节宿主 I型干扰素的应答。我院12级博士生蔡报伟为论文的第一作者。
所知的FOSL1是转录因子AP-1复合体的组分之一。然而，该研究组通过采用疟疾研究模型发现，FOSL1也能调节宿主的I型干扰素应答。研究人员深入探讨了FOSL1在I型干扰素应答的信号通路作用，证明了FOSL1可以作为I型干扰素应答的信号负调控因子。细胞受刺激后，FOSL1从主要在细胞核表达转移到胞质，并通过干扰I型干扰素应答通路的关键分子TRAF3和TRIF的K63 的多泛素化来抑制TRAF3、TRIF和TBK1之间的相互作用与信号传导。体内实验的研究结果显示，与野生型对照小鼠比较，FOSL1敲除小鼠在外周血中具有更低的疟原虫血症或水泡性口炎病毒的滴度，并降低了宿主的死亡率。因此，本研究结果揭示了FOSL1在负调节宿主I型干扰素对疟疾和病毒感染的反应中的新作用，为疟疾和其他疾病的控制与治疗提供了新的线索和思路。
原文链接：
FOSL1 Inhibits Type I Interferon Responses to Malaria and Viral Infections by Blocking TBK1 and TRAF3/TRIF Interactions
原文摘要：
Innate immune response plays a critical role in controlling invading pathogens, but such an immune response must be tightly regulated. Insufficient or overactivated immune responses may lead to harmful or even fatal consequences. To dissect the complex host-parasite interactions and the molecular mechanisms underlying innate immune responses to infections, here we investigate the role of FOS-like antigen 1 (FOSL1) in regulating the host type I interferon (IFN-I) response to malaria parasite and viral infections. FOSL1 is known as a component of a transcription factor but was recently implicated in regulating the IFN-I response to malaria parasite infection. Here we show that FOSL1 can act as a negative regulator of IFN-I signaling. Upon stimulation with poly(I:C), malaria parasite-infected red blood cells (iRBCs), or vesicular stomatitis virus (VSV), FOSL1 “translocated” from the nucleus to the cytoplasm, where it inhibited the interactions between TNF receptor-associated factor 3 (TRAF3), TIR domain-containing adapter inducing IFN-β (TRIF), and Tank-binding kinase 1 (TBK1) via impairing K63-linked polyubiquitination of TRAF3 and TRIF. Importantly, FOSL1 knockout chimeric mice had lower levels of malaria parasitemia or VSV titers in peripheral blood and decreased mortality compared with wild-type (WT) mice. Thus, our findings have identified a new role for FOSL1 in negatively regulating the host IFN-I response to malaria and viral infections and have identified a potential drug target for controlling malaria and other diseases.
作者：苏新专
