Complement component C5 is not involved in scrapie pathogenesis

The Effects of Host Age on the Transport of Complement-Bound Complexes to the Spleen and the Pathogenesis of Intravenous Scrapie Infection

“…Taken together, these data suggest that the expression of PrP C by FDCs themselves is considerably reduced in the spleens of aged mice. The abilities of FDCs to retain complement-bound complexes and express high levels of PrP c are both considered important for the trapping and amplification of TSE agents upon their surfaces (3,25,26,30,31,50). Data in the present study clearly show that both of these properties are dramatically impaired in the spleens of aged mice.…”

“…No significant difference in Prnp transcript levels were observed between the two age groups of mice (P ϭ 0.776, Mann-Whitney test). ered to be initially acquired by FDCs as complement-bound complexes (26,30,31,50). Thus, these data imply that the impaired scrapie pathogenesis in aged mice after intravenous exposure is likewise a consequence of the reduced transport of TSE agent containing complement-bound complexes from the MZ to FDCs.…”

“…Our data show that aging adversely affected the MZ microarchitecture and as a consequence substantially reduced the delivery of immune complexes to FDCs. TSE agents are likewise considered to be initially acquired by FDCs as complement-bound complexes (26,30,31,50). These data suggest the effects of aging on i.v.…”

Microglia in prion diseases

“…Overall, complement activity was upregulated in several prion-infected rodent brains in a timedependent manner, and complement components such as C1q, C3, and membrane attack complex (MAC) were also upregulated and detected in various cell types, including microglia (62). Nevertheless, the contribution of the complement system in prion-induced neurodegeneration in the CNS seems to be minor, as mice deficient in various complement components developed disease similarly to WT mice upon intracerebral challenge with prions (58,59,63).…”

C1q binding and complement activation by prions and amyloids

“…Scrapie infection via intracranial injection was not however affected by C1q-deficiency, suggesting that the critical role of complement involvement in TSE disease occurs prior to PrP Sc invasion of the CNS . Downstream components and effector systems of complement, such as C5 and the membrane attack complex, may contribute to demyelination and neural damage, but such components do not appear to affect the kinetics of disease, since scrapie susceptibility and mortality remain unaltered in C5-deficient mice (Mabbott and Bruce, 2004). …”