Incunabular immunological events in prion trafficking.
While prions probably interact with the innate immune system immediately following infection, little is known about this initial confrontation. Here we investigated incunabular events in lymphotropic and intranodal prion trafficking by following highly enriched, fluorescent prions from infection sites to draining lymph nodes. We detected biphasic lymphotropic transport of prions from the initial entry site upon peripheral prion inoculation. Prions arrived in draining lymph nodes cell autonomously within two hours of intraperitoneal administration. Monocytes and dendritic cells (DCs) required Complement for optimal prion delivery to lymph nodes hours later in a second wave of prion trafficking. B cells constituted the majority of prion-bearing cells in the mediastinal lymph node by six hours, indicating intranodal prion reception from resident DCs or subcapsulary sinus macrophages or directly from follicular conduits. These data reveal novel, cell autonomous prion lymphotropism, and a prominent role for B cells in intranodal prion movement.
College of Veterinary Medicine and Biomedical Sciences, Department of Microbiology, Immunology and Pathology, Prion Research Program at Colorado State University, Fort Collins, Colorado 80521, USA.
Brady
B
Michel
Crystal
C
Meyerett-Reid
Theodore
T
Johnson
Adam
A
Ferguson
Christy
C
Wyckoff
Bruce
B
Pulford
Heather
H
Bender
Anne
A
Avery
Glenn
G
Telling
Steven
S
Dow
Mark D
MD
Zabel
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015922:Complement C1q / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003176:Complement C3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D007107:Immune System / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D017096:Prion Diseases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011328:Prions / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D021381:Protein Transport; D013997:Time Factors
D003176:Complement C3; D011328:Prions; D015922:Complement C1q