Although A1-astrocytes are considered to be rather detrimental to neuronal health, our findings show for the first time that C3+-PrPSc-reactive-astrocytes, a prion-induced specific subtype of reactive astrocytes, might act beneficially in prion disease pathophysiology by stimulating and supporting microglia and possibly slowing the progression of prion infection throughout the brain. Here, C3 is linked to prion disease.