Activation of microglia by retroviral infection correlates with transient clearance of prions from the brain but does not change incubation time.
Brain Pathology. 2016-11-21; 27(5): 590-602
DOI: 10.1111/bpa.12441
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1. Brain Pathol. 2017 Sep;27(5):590-602. doi: 10.1111/bpa.12441. Epub 2016 Nov 21.
Activation of microglia by retroviral infection correlates with transient
clearance of prions from the brain but does not change incubation time.
Muth C(1), Schröck K(1), Madore C(2), Hartmann K(1), Fanek Z(2), Butovsky O(2),
Glatzel M(1), Krasemann S(1)(2).
Author information:
(1)Institute of Neuropathology, University Medical Center Hamburg-Eppendorf,
Hamburg, Germany.
(2)Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.
Prion diseases are fatal transmissible diseases, where conversion of the
endogenous prion protein (PrPC ) into a misfolded isoform (PrPSc ) leads to
neurodegeneration. Microglia, the immune cells of the brain, are activated in
neurodegenerative disorders including prion diseases; however, their impact on
prion disease pathophysiology is unclear with both beneficial PrPSc -clearing and
detrimental potentially neurotoxic effects. Moreover, monocytes entering the
brain from the periphery during disease course might add to disease
pathophysiology. Here, the degree of microglia activation in the brain of prion
infected mice with and without an additional intraperitoneal retrovirus infection
was studied. Peripheral murine retrovirus infection leads to activation of
parenchymal microglia without recruitment of monocytes. This activation
correlated with transient clearance or delay in accumulation of infectious prions
specifically from the brain at early time points in the diseases course.
Microglia expression profiling showed upregulation of genes involved in protein
degradation coinciding with prion clearance. This enforces a concept where
microglia act beneficial in prion disease if adequately activated. Once microglia
activation has ceased, prion disease reemerges leading to disease kinetics
undistinguishable from the situation in prion-only infected mice. This might be
caused by the loss of microglial homeostatic function at clinical prion disease.
© 2016 International Society of Neuropathology.
DOI: 10.1111/bpa.12441
PMCID: PMC6625757
PMID: 27558169 [Indexed for MEDLINE]