Genetic depletion of complement receptors CD21/35 prevents terminal prion disease in a mouse model of chronic wasting disease

Brady Michel, Adam Ferguson, Theodore Johnson, Heather Bender, Crystal Meyerett-Reid, Bruce Pulford, Adriana Von Teichman, Davis Seelig, John H. Weis, Glenn C. Telling, Adriano Aguzzi, Mark D. Zabel

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The complement system has been shown to facilitate peripheral prion pathogenesis. Mice lacking complement receptors CD21/35 partially resist terminal prion disease when infected i.p. with mouse-adapted scrapie prions. Chronic wasting disease (CWD) is an emerging prion disease of captive and free-ranging cervid populations that, similar to scrapie, has been shown to involve the immune system, which probably contributes to their relatively facile horizontal and environmental transmission. In this study, we show that mice overexpressing the cervid prion protein and susceptible to CWD (Tg(cerPrP)5037 mice) but lack CD21/35 expression completely resist clinical CWD upon peripheral infection. CD21/35-deficient Tg5037 mice exhibit greatly impaired splenic prion accumulation and replication throughout disease, similar to CD21/35-deficient murine prion protein mice infected with mouse scrapie. TgA5037;CD21/35 -/- mice exhibited little or no neuropathology and deposition of misfolded, protease-resistant prion protein associated with CWD. CD21/35 translocate to lipid rafts and mediates a strong germinal center response to prion infection that we propose provides the optimal environment for prion accumulation and replication. We further propose a potential role for CD21/35 in selecting prion quasi-species present in prion strains that may exhibit differential zoonotic potential compared with the parental strains.

Original languageEnglish (US)
Pages (from-to)4520-4527
Number of pages8
JournalJournal of Immunology
Volume189
Issue number9
DOIs
StatePublished - Nov 1 2012

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Chronic Wasting Disease
Complement Receptors
Prion Diseases
Prions
Scrapie
Germinal Center
Zoonoses
Infection
Immune System
Peptide Hydrolases
Lipids

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Michel, B., Ferguson, A., Johnson, T., Bender, H., Meyerett-Reid, C., Pulford, B., ... Zabel, M. D. (2012). Genetic depletion of complement receptors CD21/35 prevents terminal prion disease in a mouse model of chronic wasting disease. Journal of Immunology, 189(9), 4520-4527. https://doi.org/10.4049/jimmunol.1201579

Genetic depletion of complement receptors CD21/35 prevents terminal prion disease in a mouse model of chronic wasting disease. / Michel, Brady; Ferguson, Adam; Johnson, Theodore; Bender, Heather; Meyerett-Reid, Crystal; Pulford, Bruce; Von Teichman, Adriana; Seelig, Davis; Weis, John H.; Telling, Glenn C.; Aguzzi, Adriano; Zabel, Mark D.

In: Journal of Immunology, Vol. 189, No. 9, 01.11.2012, p. 4520-4527.

Research output: Contribution to journalArticle

Michel, B, Ferguson, A, Johnson, T, Bender, H, Meyerett-Reid, C, Pulford, B, Von Teichman, A, Seelig, D, Weis, JH, Telling, GC, Aguzzi, A & Zabel, MD 2012, 'Genetic depletion of complement receptors CD21/35 prevents terminal prion disease in a mouse model of chronic wasting disease', Journal of Immunology, vol. 189, no. 9, pp. 4520-4527. https://doi.org/10.4049/jimmunol.1201579
Michel, Brady ; Ferguson, Adam ; Johnson, Theodore ; Bender, Heather ; Meyerett-Reid, Crystal ; Pulford, Bruce ; Von Teichman, Adriana ; Seelig, Davis ; Weis, John H. ; Telling, Glenn C. ; Aguzzi, Adriano ; Zabel, Mark D. / Genetic depletion of complement receptors CD21/35 prevents terminal prion disease in a mouse model of chronic wasting disease. In: Journal of Immunology. 2012 ; Vol. 189, No. 9. pp. 4520-4527.
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