Abstract
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.
Highlights
Prion diseases, referred to as transmissible spongiform encephalopathies, are subacute, infectious, neurodegenerative diseases that affect humans and some domestic and free-ranging animal species to which there are no effective treatments
We focus on the peripherally-acquired prion diseases such as natural sheep scrapie, chronic wasting disease in cervid species and bovine spongiform encephalopathy (BSE) in cattle, as these are considered to be transmitted by the oral route through the ingestion of food or pasture contaminated with prions
We provide a detailed account of how inflammation, ageing and pathogen co-infection can have a significant impact on prion disease pathogenesis and susceptibility by causing changes to the abundance, function and activation status of specific immune cell populations
Summary
Referred to as transmissible spongiform encephalopathies, are subacute, infectious, neurodegenerative diseases that affect humans and some domestic and free-ranging animal species to which there are no effective treatments. Other studies revealed that this peripheral phase of prion replication in SLO such as the spleen was important for the efficient transmission of disease to the CNS [21]. These studies were soon accompanied by others that showed how modulation of the immune system around the time of peripheral exposure could have a profound influence prion disease pathogenesis [22,23,24,25]. We provide a detailed account of how inflammation, ageing and pathogen co-infection can have a significant impact on prion disease pathogenesis and susceptibility by causing changes to the abundance, function and activation status of specific immune cell populations
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