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

International Journal of Molecular Sciences

BarryM. Bradford¹  DavidS. Donaldson¹  Reiss Pal¹  NeilA. Mabbott¹  Rachel Young¹ 

[1] The Roslin Institute & Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK;

关键词: prions and prion disease;    immune system;    inflammation;    aging;    co-infection;    susceptibility;   

DOI  :  10.3390/ijms21197299

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown