Complement regulatory protein factor H is a soluble prion receptor that potentiates peripheral prion pathogenesis

Sarah J. Kane, Taylor K. Farley, Elizabeth O. Gordon, Joshua Estep, Heather R. Bender, Julie A. Moreno, Jason Bartz, Glenn C. Telling, Matthew C. Pickering, Mark D. Zabel

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Several complement proteins exacerbate prion disease, including C3, C1q, and CD21/35. These proteins of the complement cascade likely increase uptake, trafficking, and retention of prions in the lymphoreticular system, hallmark sites of early prion propagation. Complement regulatory protein factor H (fH) binds modified host proteins and lipids to prevent C3b deposition and, thus, autoimmune cell lysis. Previous reports show that fH binds various conformations of the cellular prion protein, leading us to question the role of fH in prion disease. In this article, we report that transgenic mice lacking Cfh alleles exhibit delayed peripheral prion accumulation, replication, and pathogenesis and onset of terminal disease in a gene-dose manner. We also report a biophysical interaction between purified fH and prion rods enriched from prion-diseased brain. fH also influences prion deposition in brains of infected mice. We conclude from these data and previous findings that the interplay between complement and prions likely involves a complex balance of prion sequestration and destruction via local tissue macrophages, prion trafficking by B and dendritic cells within the lymphoreticular system, intranodal prion replication by B and follicular dendritic cells, and potential prion strain selection by CD21/35 and fH. These findings reveal a novel role for complement-regulatory proteins in prion disease.

Original languageEnglish (US)
Pages (from-to)3821-3827
Number of pages7
JournalJournal of Immunology
Issue number11
StatePublished - Dec 1 2017

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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