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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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Prion Trafficking Model.Immune cells encounter prions in the PC and MedLN. Mφ, DCs, monocytes, neutrophils, B and T cells have all been shown to associate with prions in the PC and MedLN early after infection. Small prion particles traffic passively through the lymphatic system and enter the lymph node through afferent lymphatic vessels where they encounter B cells through follicular conduits. DCs may also access prions through protrusion of their dendrites through tight junctions into follicular conduits. SCS Mφs trap larger prion or prion-complement immune complexes through scavenger or complement receptor 3 and may present them to underlying follicular B cells. Inflammatory monocytes actively transport prions to SCS Mφs, B cells, or DCs in the draining lymph node. B cells facilitate intrafollicular prion trafficking to FDCs for efficient prion replication.
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f8: Prion Trafficking Model.Immune cells encounter prions in the PC and MedLN. Mφ, DCs, monocytes, neutrophils, B and T cells have all been shown to associate with prions in the PC and MedLN early after infection. Small prion particles traffic passively through the lymphatic system and enter the lymph node through afferent lymphatic vessels where they encounter B cells through follicular conduits. DCs may also access prions through protrusion of their dendrites through tight junctions into follicular conduits. SCS Mφs trap larger prion or prion-complement immune complexes through scavenger or complement receptor 3 and may present them to underlying follicular B cells. Inflammatory monocytes actively transport prions to SCS Mφs, B cells, or DCs in the draining lymph node. B cells facilitate intrafollicular prion trafficking to FDCs for efficient prion replication.

Mentions: Based on the data described here, we propose an updated, more detailed model of lymphotropic and intranodal prion trafficking by immune cells (Figure 8). Biphasic lymphotropic transport of prions occurs from the initial entry site upon peripheral prion infection. A first wave of smaller prion aggregates passively percolate through interstitia, and collect into and quickly travel through the lymphatic system to draining lymph nodes. A small number of monocytes also rapidly and actively transport larger prion aggregates. SCS MΦs capture free prions as they emerge from afferent lymphatic vessels, while resident DCs extend processes into follicular conduits and extract free prions. MΦs at the site of infection capture large and small aggregates with or without Complement, perhaps by scavenger or other phagocytic receptors, or even macropinocytosis. These peripheral MΦs more likely degrade and/or sequester the majority of prions, whereas DCs and monocytes preferentially retain Complement-opsonized prions on their cell surfaces via Complement receptors. These prDCs and prMonos deliver the second wave of prions to draining LNs at least 12 hours later.


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)

Prion Trafficking Model.Immune cells encounter prions in the PC and MedLN. Mφ, DCs, monocytes, neutrophils, B and T cells have all been shown to associate with prions in the PC and MedLN early after infection. Small prion particles traffic passively through the lymphatic system and enter the lymph node through afferent lymphatic vessels where they encounter B cells through follicular conduits. DCs may also access prions through protrusion of their dendrites through tight junctions into follicular conduits. SCS Mφs trap larger prion or prion-complement immune complexes through scavenger or complement receptor 3 and may present them to underlying follicular B cells. Inflammatory monocytes actively transport prions to SCS Mφs, B cells, or DCs in the draining lymph node. B cells facilitate intrafollicular prion trafficking to FDCs for efficient prion replication.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f8: Prion Trafficking Model.Immune cells encounter prions in the PC and MedLN. Mφ, DCs, monocytes, neutrophils, B and T cells have all been shown to associate with prions in the PC and MedLN early after infection. Small prion particles traffic passively through the lymphatic system and enter the lymph node through afferent lymphatic vessels where they encounter B cells through follicular conduits. DCs may also access prions through protrusion of their dendrites through tight junctions into follicular conduits. SCS Mφs trap larger prion or prion-complement immune complexes through scavenger or complement receptor 3 and may present them to underlying follicular B cells. Inflammatory monocytes actively transport prions to SCS Mφs, B cells, or DCs in the draining lymph node. B cells facilitate intrafollicular prion trafficking to FDCs for efficient prion replication.
Mentions: Based on the data described here, we propose an updated, more detailed model of lymphotropic and intranodal prion trafficking by immune cells (Figure 8). Biphasic lymphotropic transport of prions occurs from the initial entry site upon peripheral prion infection. A first wave of smaller prion aggregates passively percolate through interstitia, and collect into and quickly travel through the lymphatic system to draining lymph nodes. A small number of monocytes also rapidly and actively transport larger prion aggregates. SCS MΦs capture free prions as they emerge from afferent lymphatic vessels, while resident DCs extend processes into follicular conduits and extract free prions. MΦs at the site of infection capture large and small aggregates with or without Complement, perhaps by scavenger or other phagocytic receptors, or even macropinocytosis. These peripheral MΦs more likely degrade and/or sequester the majority of prions, whereas DCs and monocytes preferentially retain Complement-opsonized prions on their cell surfaces via Complement receptors. These prDCs and prMonos deliver the second wave of prions to draining LNs at least 12 hours later.

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