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Cellular prion proteins (PrP^C) are mainly expressed in the central nervous system where they have antioxidant effects and a role in the endocytosis of bacteria within cells. These proteins also have some crucial biological functions including roles in neurotransmission, signal transduction and programmed cell death. However, the role of prion proteins in neuronal Brucella infection, specifically in the interaction of the pathogen and the host cell is controversial. In the present study, the silencing of PrP^C mRNA by small interfering RNA (siRNA) transfection was investigated in human microglia cells infected with Brucella melitensis. More than 70% of prion proteins were down-regulated in microglia by siRNA transfection and this caused a slight decrease in the cellular viability of the control cells. Silencing of PrP^C suppressed the antioxidant systems, though it led to an up-regulation of pro-inflammatory cytokines such as …