Accumulating evidence shows a critical role of the complement system in facilitating attachment of prions to both B cells and FDCs and assisting in prion replication. Complement activation intensifies disease in prion-infected animals, and elimination of complement components inhibits prion accumulation, replication, and pathogenesis. Chronic wasting disease is a highly infectious prion disease of captive and fee-ranging cervid populations that has utilized the complement system for efficient peripheral prion replication and most likely efficient horizontal transmission. Here we show that complete genetic or transient pharmacological depletion of C3 prolongs incubation times and significantly delays splenic accumulation in a CWD transgenic mouse model. Using a semiquantitative prion amplification scoring system we show that C3 impacts disease progression in the early stages of disease by slowing the kinetic rate of accumulation and/or replication of PrPRES. The delayed kinetics in PrPRES replication correlates with delayed disease kinetics in mice deficient in C3. Taken together, these data support a critical role of C3 in peripheral CWD prion pathogenesis.
- Copyright © 2013 by The American Association of Immunologists, Inc.