Role of spleen macrophages in the clearance of scrapie agent early in pathogenesis

Follicular Dendritic Cell Dedifferentiation by Treatment with an Inhibitor of the Lymphotoxin Pathway Dramatically Reduces Scrapie Susceptibility

“…This would delay the subsequent transfer of infectivity via peripheral nerves into the CNS (21). However, LT␤R treatment also significantly reduced disease susceptibility, suggesting a substantial portion of the inoculum is destroyed, for example, by macrophages (4,9). These data are congruent with the suggestion that the action of macrophages on TSE pathogenesis is dose dependent: small doses of infectivity may be easily destroyed by macrophages, whereas higher doses are less easily digested and a fraction is retained.…”

Role of Interleukin-1 in Prion Disease-Associated Astrocyte Activation

“…[47][48][49][50] Hence, the more pronounced microgliosis in the IL-1RI Ϫ/Ϫ mice could be because of the reduced astrocytosis in these animals and possibly affects the deposition of PrP Sc by enhanced microglial phagocytosis of amyloid. [51][52][53][54] Our observations indicate that IL-1 acts as a driver of the scrapie-associated activation of astrocytes during early stages of the disease. Although IL-1 is clearly not essential for the development of the ultimately lethal neurodegeneration (Table 1), the experimental model suggests that therapeutic agents that suppress astrocyte activation and/or glial IL-1 expression may help to delay disease onset in established prion infections of the central nervous system.…”

Orally Administered Prion Protein Is Incorporated by M Cells and Spreads into Lymphoid Tissues with Macrophages in Prion Protein Knockout Mice

“…43 Dendritic cells and macrophages in SED would immediately degrade incorporated PrP c . 44,45 These results indicate that the undigested PrP Sc may induce the accumulation of PrP-positive cells in the subfollicle region of Peyer's patches and their spread to the MLN and the spleen.…”

“…Additionally, the depletion of spleen macrophages by administrating clodronate to mice shows that macrophages partly control scrapie infection in peripheral tissues by sequestration of the scrapie inoculum and impairment of the replication of scrapie infectious agents in the spleen during the early stages of the disease. 45 DCs 49 and macrophages 50 in Peyer's patches were previously reported to express the CD11b molecule. In addition, it has also been reported that only DCs in Peyer's patches expressed annexin V. 27 PrP-positive cells in Peyer's patches did not express annexin V in our study ( Figure 5).…”