Stromal complement receptor CD21/35 facilitates lymphoid prion colonization and pathogenesis |
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Authors: | Zabel Mark D Heikenwalder Mathias Prinz Marco Arrighi Isabelle Schwarz Petra Kranich Jan von Teichman Adriana Haas Karen M Zeller Nicolas Tedder Thomas F Weis John H Aguzzi Adriano |
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Institution: | Institute for Neuropathology, University Hospital of Zürich, Zürich, Switzerland. mark.zabel@colostate.edu |
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Abstract: | 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. |
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