Department of Pathology and Institute for Human Infection and Immunity, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77550, USA.
Virology. 2011 Mar 30;412(1):188-95. doi: 10.1016/j.virol.2011.01.012. Epub 2011 Feb 1.
Wild-type yellow fever virus (YFV) infections result in a hepatotropic disease which is often fatal, while vaccination with the live-attenuated 17-D strain results in productive infection yet is well-tolerated with few adverse events. Kupffer cells (KCs) are resident liver macrophages that have a significant role in pathogen detection, clearance and immune signaling. Although KCs appear to be an important component of YF disease, their role has been under-studied. This study examined cytokine responses in KCs following infection with either wild-type or vaccine strains of YFV. Results indicate that KCs support replication of both wild-type and vaccine strains, yet wild-type YFV induced a prominent and prolonged pro-inflammatory cytokine response (IL-8, TNF-α and RANTES/CCL5) with little control by a major anti-inflammatory cytokine (IL-10). This response was significantly reduced in vaccine strain infections. These data suggest that a differentially regulated infection in KCs may play a critical role in development of disease.
野生型黄热病病毒（YFV）感染会导致肝脏疾病，且通常是致命的，而接种减毒 17-D 株可导致生产性感染，但副作用很少。枯否细胞（KCs）是驻留于肝脏的巨噬细胞，在病原体检测、清除和免疫信号传递方面具有重要作用。尽管 KCs 似乎是 YF 疾病的重要组成部分，但它们的作用尚未得到充分研究。本研究检测了野生型或疫苗株 YFV 感染后 KCs 中的细胞因子反应。结果表明，KCs 支持野生型和疫苗株的复制，但野生型 YFV 诱导了明显且持久的促炎细胞因子反应（IL-8、TNF-α 和 RANTES/CCL5），而主要抗炎细胞因子（IL-10）的控制作用很小。疫苗株感染中的这种反应显著降低。这些数据表明，KCs 中受调控的差异感染可能在疾病发展中起关键作用。
