Experimental inoculation of CD11c⁺ B1 lymphocytes, CD68⁺ macrophages, or platelet-rich plasma from scrapie-infected sheep into susceptible sheep results in variable infectivity

Many studies have demonstrated prion infectivity in whole blood and blood components in a variety of transmissible spongiform encephalopathies of livestock and rodents, and variant Creutzfeldt-Jakob disease in humans, as well as an association between pathogenic prion protein (PrP^Sc) and different immune cells (e.g. follicular dendritic cells, T and B lymphocytes, monocytes and tingible body macrophages). To further investigate the role of various blood components in prion disease transmission, we intracranially inoculated genetically susceptible VRQ/ARQ and ARQ/ARQ sheep with inocula composed of CD11c⁺ B1 lymphocytes, CD68 +macrophages, or platelet-rich plasma derived from clinically ill sheep infected with the US no. 13-7 scrapie agent. At the completion of the study, we found that VRQ/ARQ and ARQ/ARQ sheep inoculated with CD11c⁺ B1 lymphocytes and CD68⁺ macrophages developed scrapie with detectable levels of PrP^Sc in the central nervous system and lymphoreticular system, while those inoculated with platelet-rich plasma did not develop disease and did not have detectable PrP^Sc by immunohistochemistry or enzyme immunoassay. This study complements and expands on earlier findings that white blood cells harbour prion infectivity, and reports CD11c⁺ B1 lymphocytes and CD68⁺ macrophages as additional targets for possible preclinical detection of prion infection in blood.