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

Authors: MAMMADOVA, NAJIBA - Orise Fellow; CASSMANN, ERIC - Orise Fellow; MOORE, S.JO - Orise Fellow; Nicholson, Eric; Greenlee, Justin

Submitted to: Access Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/24/2020
Publication Date: 7/28/2020
Citation: Mammadova, N., Cassmann, E., Moore, S., Nicholson, E.M., Greenlee, J.J. 2020. Experimental inoculation of CD11c+ B1 lymphocytes, CD68+ macrophages, or platelet-rich plasma from scrapie-infected sheep into susceptible sheep results in variable infectivity. Access Microbiology. 2(9). https://doi.org/10.1099/acmi.0.000155.
DOI: https://doi.org/10.1099/acmi.0.000155

Interpretive Summary: Scrapie is a fatal disease of sheep and goats that causes damaging changes in the brain. The infectious agent is an abnormal protein called a prion that has misfolded from its normal state. Previous studies have shown that immune cells isolated from blood of a prion-infected animal can transmit the disease to another animal of the same species. To expand on these studies, we inoculated specific cell types lymphocytes (B1 lymphocytes expressing CD11c), macrophages (expressing a cell surface marker called CD 68), or platelet-rich plasma from scrapie-infected sheep into susceptible sheep. At the end of the study we found that animals inoculated with CD11c+ B1 lymphocytes or CD68+ macrophages developed disease and had detectable abnormal prion protein in the brain and lymphoid system, while animals inoculated with platelet-rich plasma did not develop disease and did not have detectable abnormal prion protein in the brain or lymphoid system. This study expands on previous findings that white blood cells isolated from a sick animal can transmit prion disease. This study also has implications for the use of specific white blood cell subsets to detect prions in blood of preclinical animals that do not display outward signs of clinical illness.

Technical 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 (PrPSc) 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 PrPSc in the central nervous system and lymphoreticular system, while those inoculated with platelet-rich plasma did not develop disease and did not have detectable PrPSc by immunohistochemistry or enzyme immunoassay. This study complements and expands on earlier findings that white blood cells harbor prion infectivity, and reports CD11c+ B1 lymphocytes and CD68+ macrophages as additional targets for possible preclinical detection of prion infection in blood.