Processing of the Bovine Spongiform Encephalopathy-Specific Prion Protein by Dendritic Cells
Processing of the Bovine Spongiform Encephalopathy-Specific Prion Protein by Dendritic Cells
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树突状细胞加工牛海绵状脑病特异性朊病毒蛋白
作者：
Catherine Rybner;C. Jacquemot;Céline Cuche;G. Dore;L. Majlessi;M. Gabellec;A. Moris;O. Schwartz;J. D. Di Santo;A. Cumano;C. Leclerc;F. Lazarini
摘要 树突状细胞 (DC) 被怀疑与传染性海绵状脑病有关，包括牛海绵状脑病 (BSE)。在免疫活性小鼠腹腔内接种 BSE 朊病毒 45 天后，我们在通过磁性细胞分选纯化的脾 DC 中检测到了疾病特异性、蛋白酶抗性朊病毒蛋白 (PrPbse)。我们发现，来自野生型或 PrP 缺失小鼠的骨髓来源 DC (BMDC) 在接种 BSE 的体外培养 2 小时内获得了 PrPbse 和朊病毒感染性。 BMDC 在培养后 2 至 3 天内清除了 PrPbse，而 BMDC 感染性在培养第 1 天至第 6 天之间仅降低了 10 倍，这表明 BMDC 中感染单位的去除速度与从这些细胞中去除 PrPbse 的速度不同。当与 BSE 接种物一起孵育时，骨髓源性浆细胞样 DC 和骨髓源性巨噬细胞 (BMM) 也会获得并降解 PrPbse，其动力学与 BMDC 非常相似。 PrPbse 捕获可能对抗原呈递细胞具有特异性，因为当脾 B 或 T 淋巴细胞在体外与 BSE 接种物一起孵育时，没有观察到 PrPbse 的摄取。 BSE 感染之前 BMDC 或 BMM 的脂多糖激活导致 PrPbse 加速分解。通过腹膜内途径注射，BMDC 对于淋巴重组激活基因 20/常见细胞因子 γ 链缺陷小鼠没有感染性，表明这些细胞不能直接将 BSE 感染性传播到神经末梢。
ABSTRACT Dendritic cells (DC) are suspected to be involved in transmissible spongiform encephalopathies, including bovine spongiform encephalopathy (BSE). We detected the disease-specific, protease-resistant prion protein (PrPbse) in splenic DC purified by magnetic cell sorting 45 days after intraperitoneal inoculation of BSE prions in immunocompetent mice. We showed that bone marrow-derived DC (BMDC) from wild-type or PrP-null mice acquired both PrPbse and prion infectivity within 2 h of in vitro culture with a BSE inoculum. BMDC cleared PrPbse within 2 to 3 days of culture, while BMDC infectivity was only 10-fold diminished between days 1 and 6 of culture, suggesting that the infectious unit in BMDC is not removed at the same rate as PrPbse is removed from these cells. Bone marrow-derived plasmacytoid DC and bone marrow-derived macrophages (BMM) also acquired and degraded PrPbse when incubated with a BSE inoculum, with kinetics very similar to those of BMDC. PrPbse capture is probably specific to antigen-presenting cells since no uptake of PrPbse was observed when splenic B or T lymphocytes were incubated with a BSE inoculum in vitro. Lipopolysaccharide activation of BMDC or BMM prior to BSE infection resulted in an accelerated breakdown of PrPbse. Injected by the intraperitoneal route, BMDC were not infectious for alymphoid recombination-activated gene 20/common cytokine γ chain-deficient mice, suggesting that these cells are not capable of directly propagating BSE infectivity to nerve endings.