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

Najiba Mammadova; Eric D Cassmann; S Jo Moore; Eric M Nicholson; Justin J Greenlee

doi:10.1099/acmi.0.000155

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

Access Microbiol. 2020 Jul 28;2(9):acmi000155. doi: 10.1099/acmi.0.000155. eCollection 2020.

Authors

Najiba Mammadova^{1

2}, Eric D Cassmann^{1

2}, S Jo Moore^{1

2}, Eric M Nicholson¹, Justin J Greenlee¹

Affiliations

¹ Virus and Prion Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, Ames, IA, USA.
² Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and the U.S. Department of Agriculture (USDA). ORISE is managed by ORAU under DOE contract number DE-SC0014664.

Abstract

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.

Keywords: B lymphocytes; blood components; macrophages; platelets; prion disease; prions in blood; scrapie.