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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 immune cells trafficking prions in complement deficient mice.Figure panels are arranged similarly as in Figure 4. Pie charts to the right of the flow cytographs of prionophils from wt (f–j), C1q−/− (k–o) and C3−/− (p–t) mice represent relative frequencies of prionophils. Pie chart wedges depict MΦs from wt (red), C1q−/− (purple), and C3−/− (green) mice, DCs from wt (dotted red), C1q−/− (dotted purple), and C3−/− (dotted green) mice, monocytes from wt (striped red), C1q−/− (striped purple), and C3−/− (striped green) mice, and neutrophils (black) from wt, C1q−/−, and C3−/− mice.
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f7: Flow cytometric analysis of immune cells trafficking prions in complement deficient mice.Figure panels are arranged similarly as in Figure 4. Pie charts to the right of the flow cytographs of prionophils from wt (f–j), C1q−/− (k–o) and C3−/− (p–t) mice represent relative frequencies of prionophils. Pie chart wedges depict MΦs from wt (red), C1q−/− (purple), and C3−/− (green) mice, DCs from wt (dotted red), C1q−/− (dotted purple), and C3−/− (dotted green) mice, monocytes from wt (striped red), C1q−/− (striped purple), and C3−/− (striped green) mice, and neutrophils (black) from wt, C1q−/−, and C3−/− mice.

Mentions: While C1q−/− and C3−/− mice possessed similar numbers of total prionophils in the PC, they exhibited altered prionophil proportions compared to controls (Figure 7, panels f, k, p, and u). We detected fewer prDCs from C1q−/− (panels 6n and x, median = 390; IQR = 184 to 1077 n = 11, p = 0.01) or C3−/− mice (6s and x, median = 913; IQR = 165 to 1492 n = 7, p = 0.01) than from wt mice (6i and x, median = 3089; IQR = 982 to 33614 n = 17, p = 0.001). Concomitantly, we observed increases in prNeuts from C1q−/− (6m and w, median 4006; IQR = 296 to 8508 n = 11, p = 0.01) and C3−/− (6r and w, median 2420; IQR = 1383 to 10098 n = 7, p = 0.05) mice compared to wt mice (6h and w, median 93; IQR = 42 to 6669 n = 11, p = 0.001). Consequently, the proportion of prDCs in the PC decreased 8.4-fold in C1q−/− (Figure 7, pie chart right of panel O, dotted purple wedge) and two-fold in C3−/− mice (dotted green wedge from panel T pie chart) compared to wt (dotted red wedge from Panel J pie chart), while prNeut proportions increased 40.6 and 21-fold for C1q−/− and C3−/− mice, respectively (compare black wedges in the three pie charts right of j, o and t). We also detected a two-fold decrease in prMonos from C3−/− (striped green) but not C1q−/− (striped purple) mice compared to wt (striped red). We detected no significant proportional changes in prMΦs (solid colored wedges), which remained the predominant prion scavenger in the PC of wt (j and y), C1q−/− (o and y) and C3−/− (t and y) mice.


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 immune cells trafficking prions in complement deficient mice.Figure panels are arranged similarly as in Figure 4. Pie charts to the right of the flow cytographs of prionophils from wt (f–j), C1q−/− (k–o) and C3−/− (p–t) mice represent relative frequencies of prionophils. Pie chart wedges depict MΦs from wt (red), C1q−/− (purple), and C3−/− (green) mice, DCs from wt (dotted red), C1q−/− (dotted purple), and C3−/− (dotted green) mice, monocytes from wt (striped red), C1q−/− (striped purple), and C3−/− (striped green) mice, and neutrophils (black) from wt, C1q−/−, and C3−/− mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7: Flow cytometric analysis of immune cells trafficking prions in complement deficient mice.Figure panels are arranged similarly as in Figure 4. Pie charts to the right of the flow cytographs of prionophils from wt (f–j), C1q−/− (k–o) and C3−/− (p–t) mice represent relative frequencies of prionophils. Pie chart wedges depict MΦs from wt (red), C1q−/− (purple), and C3−/− (green) mice, DCs from wt (dotted red), C1q−/− (dotted purple), and C3−/− (dotted green) mice, monocytes from wt (striped red), C1q−/− (striped purple), and C3−/− (striped green) mice, and neutrophils (black) from wt, C1q−/−, and C3−/− mice.
Mentions: While C1q−/− and C3−/− mice possessed similar numbers of total prionophils in the PC, they exhibited altered prionophil proportions compared to controls (Figure 7, panels f, k, p, and u). We detected fewer prDCs from C1q−/− (panels 6n and x, median = 390; IQR = 184 to 1077 n = 11, p = 0.01) or C3−/− mice (6s and x, median = 913; IQR = 165 to 1492 n = 7, p = 0.01) than from wt mice (6i and x, median = 3089; IQR = 982 to 33614 n = 17, p = 0.001). Concomitantly, we observed increases in prNeuts from C1q−/− (6m and w, median 4006; IQR = 296 to 8508 n = 11, p = 0.01) and C3−/− (6r and w, median 2420; IQR = 1383 to 10098 n = 7, p = 0.05) mice compared to wt mice (6h and w, median 93; IQR = 42 to 6669 n = 11, p = 0.001). Consequently, the proportion of prDCs in the PC decreased 8.4-fold in C1q−/− (Figure 7, pie chart right of panel O, dotted purple wedge) and two-fold in C3−/− mice (dotted green wedge from panel T pie chart) compared to wt (dotted red wedge from Panel J pie chart), while prNeut proportions increased 40.6 and 21-fold for C1q−/− and C3−/− mice, respectively (compare black wedges in the three pie charts right of j, o and t). We also detected a two-fold decrease in prMonos from C3−/− (striped green) but not C1q−/− (striped purple) mice compared to wt (striped red). We detected no significant proportional changes in prMΦs (solid colored wedges), which remained the predominant prion scavenger in the PC of wt (j and y), C1q−/− (o and y) and C3−/− (t and y) mice.

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