Targeting of prion-infected lymphoid cells to the central nervous system accelerates prion infection

Background: prions,composed of a misfolded protein designated prp sc,are infectious agents causing fatal neurodegenerative diseases. we have shown previously that,following induction of experimental autoimmune encephalomyelitis,prion-infected mice succumb to disease significantly earlier than controls,concomitant with the deposition of prp scaggregates in inflamed white matter areas. in the present work,we asked whether prion disease acceleration by experimental autoimmune encephalomyelitis results from infiltration of viable prion-infected immune cells into the central nervous system.methods: c57bl/6 j mice underwent intraperitoneal inoculation with scrapie brain homogenates and were later induced with experimental autoimmune encephalomyelitis by inoculation of mog 35-55in complete freund's adjuvant supplemented with pertussis toxin. spleen and lymph node cells from the co-induced animals were reactivated and subsequently injected into naïve mice as viable cells or as cell homogenates. control groups were infected with viable and homogenized scrapie immune cells only with complete freund's adjuvant. prion disease incubation times as well as levels and sites of prp scdeposition were next evaluated.results: we first show that acceleration of prion disease by experimental autoimmune encephalomyelitis requires the presence of high levels of spleen prp sc. next,we present evidence that mice infected with activated prion-experimental autoimmune encephalomyelitis viable cells succumb to prion disease considerably faster than do mice infected with equivalent cell extracts or other controls,concomitant with the deposition of prp scaggregates in white matter areas in brains and spinal cords.conclusions: our results indicate that inflammatory targeting of viable prion-infected immune cells to the central nervous system accelerates prion disease propagation. we also show that in the absence of such targeting it is the load of prp scin the inoculum that determines the infectivity titers for subsequent transmissions. both of these conclusions have important clinical implications as related to the risk of prion disease contamination of blood products. © 2012 friedman-levi et al; licensee biomed central ltd.