Zhu Caihong, Herrmann Uli S, Li Bei, Abakumova Irina, Moos Rita, Schwarz Petra, Rushing Elisabeth J, Colonna Marco, Aguzzi Adriano
Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
Neurobiol Aging. 2015 May;36(5):1994-2003. doi: 10.1016/j.neurobiolaging.2015.02.019. Epub 2015 Feb 27.
Dysfunctional variants of the innate immune cell surface receptor TREM2 (triggering receptor expressed on myeloid cells-2) were identified as major genetic risk factors for Alzheimer's disease and other neurodegenerative conditions. Here we assessed a possible involvement of TREM2 in prion disease. We report that TREM2 expression by microglia is significantly up-regulated upon prion infection. However, depletion of TREM2 did not affect disease incubation time and survival after intracerebral prion infection. Interestingly, markers of microglial activation were attenuated in prion-infected TREM2(-/-) mice, suggesting an involvement of TREM2 in prion-induced microglial activation. Further phenotype profiling of microglia revealed that TREM2 deficiency did not change microglial phenotypes. We conclude that TREM2 is involved in prion-induced microglial activation but does not noticeably modulate the pathogenesis of experimental prion infections.
先天性免疫细胞表面受体TREM2（髓样细胞表达的触发受体-2）的功能失调变体被确定为阿尔茨海默病和其他神经退行性疾病的主要遗传风险因素。在此，我们评估了TREM2在朊病毒疾病中的可能作用。我们报告，朊病毒感染后，小胶质细胞中TREM2的表达显著上调。然而，TREM2缺失并不影响脑内朊病毒感染后的疾病潜伏期和生存期。有趣的是，在朊病毒感染的TREM2基因敲除小鼠中，小胶质细胞激活标志物减弱，这表明TREM2参与了朊病毒诱导的小胶质细胞激活。对小胶质细胞的进一步表型分析显示，TREM2缺乏并未改变小胶质细胞表型。我们得出结论，TREM2参与了朊病毒诱导的小胶质细胞激活，但并未显著调节实验性朊病毒感染的发病机制。
