Stromal complement receptor CD21/35 facilitates lymphoid prion colonization and pathogenesis.
We have studied the role of CD21/35, which bind derivatives of complement factors C3 and C4, in extraneural prion replication and neuroinvasion. Upon administration of small prion inocula, CD21/35(-/-) mice experienced lower attack rates and delayed disease over both wild-type (WT) mice and mice with combined C3 and C4 deficiencies. Early after inoculation, CD21/35(-/-) spleens were devoid of infectivity. Reciprocal adoptive bone marrow transfers between WT and CD21/35(-/-) mice revealed that protection from prion infection resulted from ablation of stromal, but not hemopoietic, CD21/35. Further adoptive transfer experiments between WT mice and mice devoid of both the cellular prion protein PrP(C) and CD21/35 showed that splenic retention of inoculum depended on stromal CD21/35 expression. Because both PrP(C) and CD21/35 are highly expressed on follicular dendritic cells, CD21/35 appears to be involved in targeting prions to follicular dendritic cells and expediting neuroinvasion following peripheral exposure to prions.
Zabel
Mark D
MD
Institute for Neuropathology, University Hospital of Zürich, Zürich, Switzerland. mark.zabel@colostate.edu
Heikenwalder
Mathias
M
Prinz
Marco
M
Arrighi
Isabelle
I
Schwarz
Petra
P
Kranich
Jan
J
von Teichman
Adriana
A
Haas
Karen M
KM
Zeller
Nicolas
N
Tedder
Thomas F
TF
Weis
John H
JH
Aguzzi
Adriano
A
D000818:Animals; D018450:Disease Progression; D008024:Ligands; D008221:Lymphoid Tissue / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011328:Prions / Q000378:metabolism* / Q000472:pathogenicity*; D017463:Receptors, Complement 3b / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017464:Receptors, Complement 3d / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism*; D013997:Time Factors
D008024:Ligands; D011328:Prions; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d