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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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Flow cytometric analysis of B cell subsets in transport of prion rods.Adoptive transfer experiment was performed similarly as experiments in Figure 5. Prion rods were injected IP into donor mice and six hours later immune cells harvested from the PC were washed and transferred into the PC of recipient mice. MedLN from donor (panels a–e) and recipient mice (panels f–h) were analyzed 6 HPI for prion-bearing B1 and B2 cells. Donor MedLN cells were analyzed for SSCloCD21+B220+CD5−CD11b-CD23+ follicular B2 cells (b and d) and SSCloB220− CD21−CD23−CD11b+CD5+ B-1 cells (c and e) bearing prion rods. Recipient MedLNs were also analyzed for prion uptake by B2 cells (red peak (g) and dots (h)) and B1 cells (green). B cell subsets were compared to cells in MedLN from PBS inoculated control mice (blue). Cell counts in graphs are shown as log10 per 105 total cells (d and e) or per 104 B cells (h).
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f6: Flow cytometric analysis of B cell subsets in transport of prion rods.Adoptive transfer experiment was performed similarly as experiments in Figure 5. Prion rods were injected IP into donor mice and six hours later immune cells harvested from the PC were washed and transferred into the PC of recipient mice. MedLN from donor (panels a–e) and recipient mice (panels f–h) were analyzed 6 HPI for prion-bearing B1 and B2 cells. Donor MedLN cells were analyzed for SSCloCD21+B220+CD5−CD11b-CD23+ follicular B2 cells (b and d) and SSCloB220− CD21−CD23−CD11b+CD5+ B-1 cells (c and e) bearing prion rods. Recipient MedLNs were also analyzed for prion uptake by B2 cells (red peak (g) and dots (h)) and B1 cells (green). B cell subsets were compared to cells in MedLN from PBS inoculated control mice (blue). Cell counts in graphs are shown as log10 per 105 total cells (d and e) or per 104 B cells (h).

Mentions: We also performed adoptive transfer experiments at 6 HPI to analyze MedLN cells for prB cells to assess the drastic increase in their proportions at this time point. In donor MedLNs we detected significant numbers of prionophilic SSCloCD5-CD11b-B220+CD23+CD21+ follicular B2 cells (prB2, Figure 6b and D, median = 24; IQR = 3 to 40, n = 5, p = 0.008). Surprisingly, we also detected significant numbers of prionophilic SSCloB220-CD21-CD23-CD11b+CD5+ B1 cells (prB1, Figure 6c and e, median = 7; IQR 4 to 21, n = 7, p = 0.005) there. MedLNs from recipient mice contained prB2 (Figure 6g and h, red peak and dots, median = 108 per 104 B cells, IQR = 41 to 179, p = 0.045), but not prB1 (green, median = 1, IQR = 1 to 29) cells 6 HPI.


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)

Flow cytometric analysis of B cell subsets in transport of prion rods.Adoptive transfer experiment was performed similarly as experiments in Figure 5. Prion rods were injected IP into donor mice and six hours later immune cells harvested from the PC were washed and transferred into the PC of recipient mice. MedLN from donor (panels a–e) and recipient mice (panels f–h) were analyzed 6 HPI for prion-bearing B1 and B2 cells. Donor MedLN cells were analyzed for SSCloCD21+B220+CD5−CD11b-CD23+ follicular B2 cells (b and d) and SSCloB220− CD21−CD23−CD11b+CD5+ B-1 cells (c and e) bearing prion rods. Recipient MedLNs were also analyzed for prion uptake by B2 cells (red peak (g) and dots (h)) and B1 cells (green). B cell subsets were compared to cells in MedLN from PBS inoculated control mice (blue). Cell counts in graphs are shown as log10 per 105 total cells (d and e) or per 104 B cells (h).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Flow cytometric analysis of B cell subsets in transport of prion rods.Adoptive transfer experiment was performed similarly as experiments in Figure 5. Prion rods were injected IP into donor mice and six hours later immune cells harvested from the PC were washed and transferred into the PC of recipient mice. MedLN from donor (panels a–e) and recipient mice (panels f–h) were analyzed 6 HPI for prion-bearing B1 and B2 cells. Donor MedLN cells were analyzed for SSCloCD21+B220+CD5−CD11b-CD23+ follicular B2 cells (b and d) and SSCloB220− CD21−CD23−CD11b+CD5+ B-1 cells (c and e) bearing prion rods. Recipient MedLNs were also analyzed for prion uptake by B2 cells (red peak (g) and dots (h)) and B1 cells (green). B cell subsets were compared to cells in MedLN from PBS inoculated control mice (blue). Cell counts in graphs are shown as log10 per 105 total cells (d and e) or per 104 B cells (h).
Mentions: We also performed adoptive transfer experiments at 6 HPI to analyze MedLN cells for prB cells to assess the drastic increase in their proportions at this time point. In donor MedLNs we detected significant numbers of prionophilic SSCloCD5-CD11b-B220+CD23+CD21+ follicular B2 cells (prB2, Figure 6b and D, median = 24; IQR = 3 to 40, n = 5, p = 0.008). Surprisingly, we also detected significant numbers of prionophilic SSCloB220-CD21-CD23-CD11b+CD5+ B1 cells (prB1, Figure 6c and e, median = 7; IQR 4 to 21, n = 7, p = 0.005) there. MedLNs from recipient mice contained prB2 (Figure 6g and h, red peak and dots, median = 108 per 104 B cells, IQR = 41 to 179, p = 0.045), but not prB1 (green, median = 1, IQR = 1 to 29) cells 6 HPI.

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