Brain Endothelial-and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment. Immunity 2016, 44:901-912.

報告日期: 2017/10/03
報告時間: 16:00/16:50
報告學生: 蔡孟珊
講評老師: 余佳益
附件下載: 下載[1657-1506044402-1.pdf] 

Brain endothelial-and epithelial-specific interferon receptor chain 1 drives virus-induced sickness behavior and cognitive impairment

Thomas B. et al., Immunity (2016) 44: 901-912

Speaker: Meng-Shan Tsai (蔡孟珊)                              Time: 16:00~16:50, Oct. 03, 2017

Commentator: Dr. Chia-Yi Yu (余佳益老師)         Place: Room 602


In response to virus infection, innate immune cells produce cytokines that act on neuron system to cause sickness behavior [1]. Cytokines, especially type I interferons, as a therapeutic application has been widely used in humans with virus infection, malignancies, malignant melanoma, or multiple sclerosis. In addition to their beneficence, there are some common side effects, including depression-like behavior, such as fatigue, insomnia, irritability, and reduced appetite and even cognitive impairment [2, 3]. However, the hidden mechanism in the communication between immune system and behavior is rarely characterized. To investigate the role of interferon-β (IFN-β) in virus infection, the authors tested vesicular stomatitis virus (VSV)-infected mice and found that depression-like behavior detected by force swim test corresponded to the dramatic elevation levels of IFN-β in circulation in the absence of VSV infection in the brain. Similar behavioral disturbances were observed in mice treated with 5’-triphasphate RNA molecules and poly (I:C), which involved in the signal cascade, RIG-I, MDA5, and MAVS. Conversely, depression-like behavior and cognitive dysfunction were absent in mice with deletion of type I interferon receptor in brain endothelia and epithelia. Moreover, the authors proved that systemic IFN-β stimulated brain endothelial and epithelial cells through type I interferon receptor, which resulted in the secretion of CXCL10 and the activation of neuronal CXCR3 signaling to decrease synaptic activity thereby contributing to depression-like behavior. Collectively, IFN-β on behalf of immune system delivers the bug link to the central nervous system in response to pathogen invasion. More importantly, this report might provide strategies to improve the management of behavior changes during viral infection and type I interferon therapy.


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  2. Walther, al.,Multiple sclerosis: side effects of interferon beta therapy and their management. Neurology (1999) 53: 1622-1627
  3. Raison, al., Cytokine sing the blue: inflammation and the pathogenesis of depression. Trends Immunol. (2006) 27: 24-31