Abstract
BackgroundIn human and animal prion diseases, pathological prion protein, PrPSc, as well as prion infectivity is mainly found in the central nervous system, but also in lymphoid organs and muscle. Pathophysiology of prion colonization of lymphoid organs has been studied intensively, yet how myositis influences prion accumulation in muscle is unknown.ResultWe have investigated the influence of myositis on PrPSc accumulation and prion infectivity in two distinct mouse models of experimental autoimmune myositis. Furthermore, we have addressed the relevance of PrPC expression in the lymphoreticular system in myositis by generating bone marrow chimeras.Here we show that myositis positively influences muscular PrPSc accumulation at preclinical time points and that PrPC-expression in the lymphoid system is critical for this. In muscle, PrPSc and prion infectivity are uncoupled with detectable PrPSc but no prion infectivity at preclinical time points. Muscle has an intrinsically high ability to clear PrPSc once myositis has ceased, possibly involving autophagy.ConclusionOur findings provide new insights into the pathophysiology of prion colonization in muscle pointing out that myositis leads to enhanced prion colonization of muscle in subclinical prion disease.Electronic supplementary materialThe online version of this article (doi:10.1186/2051-5960-1-78) contains supplementary material, which is available to authorized users.
Highlights
In human and animal prion diseases, pathological prion protein, PrPSc, as well as prion infectivity is mainly found in the central nervous system, and in lymphoid organs and muscle
PrPSc and prion infectivity are readily detectable in the lymphoreticular system (LRS) in the majority of instances, whereas prion accumulation in muscle occurs to a lesser extent both quantitatively and qualitatively [15,16,17,18]
In SJL/J mice experimental autoimmune myositis (EAM) was induced by subcutaneous injection of myosin and Complete Freund's adjuvant (CFA) at days 0, 7 and 14
Summary
In human and animal prion diseases, pathological prion protein, PrPSc, as well as prion infectivity is mainly found in the central nervous system, and in lymphoid organs and muscle. Pathophysiology of prion colonization of lymphoid organs has been studied intensively, yet how myositis influences prion accumulation in muscle is unknown. PrPSc and prion infectivity are inevitably detectable in the lymphoreticular system (LRS) or in the skeletal muscle of terminally diseased individuals or animals [10,11,12,13,14]. PrPSc and prion infectivity are readily detectable in the LRS in the majority of instances, whereas prion accumulation in muscle occurs to a lesser extent both quantitatively and qualitatively [15,16,17,18]. Peripheral nerves or muscle spindles or myocytes, have been shown to accumulate PrPSc even in the absence of inflammation [13,15,31]
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