College of Veterinary Medicine and Biomedical Sciences, Department of Microbiology, Immunology and Pathology, Prion Research Program at Colorado State University, Fort Collins, Colorado 80521, USA.
Sci Rep. 2012;2:440. doi: 10.1038/srep00440. Epub 2012 Jun 6.
While prions probably interact with the innate immune system immediately following infection, little is known about this initial confrontation. Here we investigated incunabular events in lymphotropic and intranodal prion trafficking by following highly enriched, fluorescent prions from infection sites to draining lymph nodes. We detected biphasic lymphotropic transport of prions from the initial entry site upon peripheral prion inoculation. Prions arrived in draining lymph nodes cell autonomously within two hours of intraperitoneal administration. Monocytes and dendritic cells (DCs) required Complement for optimal prion delivery to lymph nodes hours later in a second wave of prion trafficking. B cells constituted the majority of prion-bearing cells in the mediastinal lymph node by six hours, indicating intranodal prion reception from resident DCs or subcapsulary sinus macrophages or directly from follicular conduits. These data reveal novel, cell autonomous prion lymphotropism, and a prominent role for B cells in intranodal prion movement.
虽然朊病毒可能在感染后立即与先天免疫系统相互作用，但对于这种初始对抗知之甚少。在这里，我们通过从感染部位追踪高度富集的荧光朊病毒，研究了淋巴亲和性和淋巴结内朊病毒的早期事件。我们检测到外周朊病毒接种后，朊病毒从初始进入部位呈双相性淋巴亲和性转移。在腹腔内给药后两小时内，朊病毒自主到达引流淋巴结。单核细胞和树突状细胞（DC）需要补体才能在数小时后的第二波朊病毒运输中最佳地将朊病毒递送至淋巴结。在 6 小时时，B 细胞成为纵隔淋巴结中携带朊病毒的大多数细胞，表明来自驻留的 DC 或被膜下窦巨噬细胞或直接来自滤泡导管的淋巴结内朊病毒接收。这些数据揭示了新型的、自主的朊病毒淋巴亲嗜性，以及 B 细胞在淋巴结内朊病毒运动中的突出作用。
