Immune system and peripheral nerves in propagation of prions to CNS.
Prions are not only unique in the way they replicate. Also the sequence of events triggered by peripheral prion infection, generically termed 'peripheral pathogenesis', sets prions aside from all other known pathogens. Whereas most bacteria, parasites, and viruses trigger innate and adaptive immune responses, the mammalian immune system appears to be remarkably oblivious to prions. Transmissible spongiform encephalopathies (TSEs) do not go along with inflammatory infiltrates, and antibodies to the prion protein are not typically raised during the course of the disease. On the other hand, there is conspicuous involvement of lymphoid organs, which accumulate sizeable concentrations of the infectious agent early during disease. Moreover, various states of immune deficiency can abolish peripheral pathogenesis and prevent 'take' of infection when prions are administered to peripheral sites. Here, we critically re-visit the current evidence for an involvement of the immune system in prion diseases, and will attempt to trace the elaborate mechanisms by which prions, upon entry into the body from peripheral sites, reach the brain.
Aguzzi
Adriano
A
Institute of Neuropathology, Universitätsspital Zürich, Switzerland.
Heppner
Frank L
FL
Heikenwalder
Mathias
M
Prinz
Marco
M
Mertz
Kirsten
K
Seeger
Harald
H
Glatzel
Markus
M
D000682:Amyloid / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002490:Central Nervous System / Q000378:metabolism*; D006224:Cricetinae; D004261:DNA Replication; D020566:Dendritic Cells, Follicular / Q000502:physiology; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007114:Immunization; D007413:Intestinal Mucosa / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D017933:Peripheral Nervous System / Q000378:metabolism*; D017096:Prion Diseases / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D012107:Research Design; D012756:Sheep; D012867:Skin / Q000276:immunology; D013154:Spleen / Q000276:immunology
D000682:Amyloid; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D011498:Protein Precursors