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Incunabular immunological events in prion trafficking.

Michel B, Meyerett-Reid C, Johnson T, Ferguson A, Wyckoff C, Pulford B, Bender H, Avery A, Telling G, Dow S, Zabel MD - Sci Rep (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

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Related in: MedlinePlus

Analysis of monocytes capturing prion rods in the PC by confocal microscopy.PBS and prion rods (labeled red) were injected into the PC of mice and CD11b+Ly6C+ (labeled blue and green, respectively) monocytes were analyzed for prion retention. Z stack images were collected at 0.28 μm intervals and range from 0.64 to 7.31 μm. Image shown in row three, column six indicates isotype and PBS controls. Bottom row starting from the left show single stains of the nucleus (white), Ly6C, CD11b, and prion rods. The Last 2 panels in the bottom row represent a merged z stack image and an orthogonal image.
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f4: Analysis of monocytes capturing prion rods in the PC by confocal microscopy.PBS and prion rods (labeled red) were injected into the PC of mice and CD11b+Ly6C+ (labeled blue and green, respectively) monocytes were analyzed for prion retention. Z stack images were collected at 0.28 μm intervals and range from 0.64 to 7.31 μm. Image shown in row three, column six indicates isotype and PBS controls. Bottom row starting from the left show single stains of the nucleus (white), Ly6C, CD11b, and prion rods. The Last 2 panels in the bottom row represent a merged z stack image and an orthogonal image.

Mentions: We assessed subcellular location of captured prions by visulaizing peritoneal prionophils by confocal microscopy. While prMonos (Figure 4) and prMΦs (Figure S2) showed a tendency to internalize prion rods, these cells, as well as prDCs (Figure S3), and prNeuts (Figure S4) demonstrated the ability to retain prion rods on both the cell surface and intracellular compartments. Internalized fluorescent prions generally appeared more diffuse, while cell surface prions appeared as bright, punctate fluorescent aggregates ranging in size from 1 -3 µm3 on cell surfaces.


Incunabular immunological events in prion trafficking.

Michel B, Meyerett-Reid C, Johnson T, Ferguson A, Wyckoff C, Pulford B, Bender H, Avery A, Telling G, Dow S, Zabel MD - Sci Rep (2012)

Analysis of monocytes capturing prion rods in the PC by confocal microscopy.PBS and prion rods (labeled red) were injected into the PC of mice and CD11b+Ly6C+ (labeled blue and green, respectively) monocytes were analyzed for prion retention. Z stack images were collected at 0.28 μm intervals and range from 0.64 to 7.31 μm. Image shown in row three, column six indicates isotype and PBS controls. Bottom row starting from the left show single stains of the nucleus (white), Ly6C, CD11b, and prion rods. The Last 2 panels in the bottom row represent a merged z stack image and an orthogonal image.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368226&req=5

f4: Analysis of monocytes capturing prion rods in the PC by confocal microscopy.PBS and prion rods (labeled red) were injected into the PC of mice and CD11b+Ly6C+ (labeled blue and green, respectively) monocytes were analyzed for prion retention. Z stack images were collected at 0.28 μm intervals and range from 0.64 to 7.31 μm. Image shown in row three, column six indicates isotype and PBS controls. Bottom row starting from the left show single stains of the nucleus (white), Ly6C, CD11b, and prion rods. The Last 2 panels in the bottom row represent a merged z stack image and an orthogonal image.
Mentions: We assessed subcellular location of captured prions by visulaizing peritoneal prionophils by confocal microscopy. While prMonos (Figure 4) and prMΦs (Figure S2) showed a tendency to internalize prion rods, these cells, as well as prDCs (Figure S3), and prNeuts (Figure S4) demonstrated the ability to retain prion rods on both the cell surface and intracellular compartments. Internalized fluorescent prions generally appeared more diffuse, while cell surface prions appeared as bright, punctate fluorescent aggregates ranging in size from 1 -3 µm3 on cell surfaces.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus