Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
PLoS Pathog. 2011 Sep;7(9):e1002246. doi: 10.1371/journal.ppat.1002246. Epub 2011 Sep 15.
Under normal conditions the immune system has limited access to the brain; however, during toxoplasmic encephalitis (TE), large numbers of T cells and APCs accumulate within this site. A combination of real time imaging, transgenic reporter mice, and recombinant parasites allowed a comprehensive analysis of CD11c+ cells during TE. These studies reveal that the CNS CD11c+ cells consist of a mixture of microglia and dendritic cells (DCs) with distinct behavior associated with their ability to interact with parasites or effector T cells. The CNS DCs upregulated several chemokine receptors during TE, but none of these individual receptors tested was required for migration of DCs into the brain. However, this process was pertussis toxin sensitive and dependent on the integrin LFA-1, suggesting that the synergistic effect of signaling through multiple chemokine receptors, possibly leading to changes in the affinity of LFA-1, is involved in the recruitment/retention of DCs to the CNS and thus provides new insights into how the immune system accesses this unique site.
在正常情况下，免疫系统对大脑的访问受到限制；然而，在弓形体脑炎 (TE) 期间，大量的 T 细胞和 APC 在该部位积累。实时成像、转基因报告小鼠和重组寄生虫的组合允许对 TE 期间的 CD11c+细胞进行全面分析。这些研究表明，CNS CD11c+细胞由小胶质细胞和树突状细胞 (DC) 的混合物组成，它们的行为与与寄生虫或效应 T 细胞相互作用的能力相关。在 TE 期间，CNS DCs 上调了几种趋化因子受体，但在测试的这些单个受体中，没有一个是 DC 迁移到大脑所必需的。然而，这个过程对百日咳毒素敏感，并且依赖于整合素 LFA-1，这表明通过多个趋化因子受体进行信号传递的协同作用，可能导致 LFA-1 的亲和力发生变化，参与了 DC 向 CNS 的募集/保留，从而为免疫系统如何进入这一独特部位提供了新的见解。
