The Effects of Immune System Modulation on Prion Disease Susceptibility and Pathogenesis.

The Effects of Immune System Modulation on Prion Disease Susceptibility and Pathogenesis.
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DOI:
10.3390/ijms21197299
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发表时间:
2020-10-02
影响因子:
5.6
通讯作者:
Donaldson DS
Donaldson DS
中科院分区:
生物学2区
文献类型:
--
作者:
Mabbott NA;Bradford BM;Pal R;Young R;Donaldson DS

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Prion diseases are a unique group of infectious chronic neurodegenerative disorders to which there are no cures. Although prion infections do not stimulate adaptive immune responses in infected individuals, the actions of certain immune cell populations can have a significant impact on disease pathogenesis. After infection, the targeting of peripherally-acquired prions to specific immune cells in the secondary lymphoid organs (SLO), such as the lymph nodes and spleen, is essential for the efficient transmission of disease to the brain. Once the prions reach the brain, interactions with other immune cell populations can provide either host protection or accelerate the neurodegeneration. In this review, we provide a detailed account of how factors such as inflammation, ageing and pathogen co-infection can affect prion disease pathogenesis and susceptibility. For example, we discuss how changes to the abundance, function and activation status of specific immune cell populations can affect the transmission of prion diseases by peripheral routes. We also describe how the effects of systemic inflammation on certain glial cell subsets in the brains of infected individuals can accelerate the neurodegeneration. A detailed understanding of the factors that affect prion disease transmission and pathogenesis is essential for the development of novel intervention strategies.
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