title: Triggering receptor expressed on myeloid cells-2 is involved in prion-induced microglial activation but does not contribute to prion pathogenesis in mouse brains.
abstract: 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.
authors: Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland. Electronic address: Caihong.Zhu@usz.ch.
authors: Caihong
authors: C
authors: Zhu
authors: Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
authors: Uli S
authors: US
authors: Herrmann
authors: Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
authors: Bei
authors: B
authors: Li
authors: Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
authors: Irina
authors: I
authors: Abakumova
authors: Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
authors: Rita
authors: R
authors: Moos
authors: Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
authors: Petra
authors: P
authors: Schwarz
authors: Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
authors: Elisabeth J
authors: EJ
authors: Rushing
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors: Marco
authors: M
authors: Colonna
authors: Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland. Electronic address: Adriano.Aguzzi@usz.ch.
authors: Adriano
authors: A
authors: Aguzzi
mesh_terms: D000818:Animals; D015870:Gene Expression / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000502:physiology*; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D017096:Prion Diseases / Q000235:genetics*; D011971:Receptors, Immunologic / Q000502:physiology*; D012307:Risk Factors; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C498716:Trem2 protein, mouse
keywords: Microglial activation; Neuroinflammation; Pathogenesis; Prion disease; TREM2