Leisewitz Andrew L, Rockett Kirk A, Gumede Bonginkosi, Jones Margaret, Urban Britta, Kwiatkowski Dominic P
Weatherall Institute of of Molecular Medicine, and University Department of Paediatrics, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Infect Immun. 2004 Jul;72(7):4233-9. doi: 10.1128/IAI.72.7.4233-4239.2004.
Dendritic cells, particularly those residing in the spleen, are thought to orchestrate acquired immunity to malaria, but it is not known how the splenic dendritic cell population responds to malaria infection and how this response compares with the responses of other antigen-presenting cells. We investigated this question for Plasmodium chabaudi AS infection in C57BL/6 mice. We found that dendritic cells, defined here by the CD11c marker, migrated from the marginal zone of the spleen into the CD4(+) T-cell area within 5 days after parasites entered the bloodstream. This contrasted with the results observed for the macrophage and B-cell populations, which expanded greatly but did not show any comparable migration. Over the same time period dendritic cells showed upregulation of CD40, CD54, and CD86 costimulatory molecules that are required for successful T-cell activation. In dendritic cells, the peak intracellular gamma interferon expression (as shown by fluorescence-activated cell sorting) was on day 5, 2 days earlier than the peak expression in B-cells or macrophages. These findings show that splenic dendritic cells are actively engaged in the earliest phase of malarial infection in vivo and are likely to be critical in shaping the subsequent immune response.
树突状细胞，尤其是那些存在于脾脏中的树突状细胞，被认为在协调对疟疾的获得性免疫中发挥作用，但目前尚不清楚脾脏树突状细胞群体如何对疟疾感染作出反应，以及这种反应与其他抗原呈递细胞的反应相比如何。我们针对C57BL/6小鼠感染查巴迪疟原虫AS的情况研究了这个问题。我们发现，由CD11c标志物定义的树突状细胞在寄生虫进入血液后5天内从脾脏边缘区迁移至CD4(+) T细胞区。这与巨噬细胞和B细胞群体的观察结果形成对比，后者大量扩增但未表现出任何类似的迁移。在同一时间段内，树突状细胞出现了成功激活T细胞所需的共刺激分子CD40、CD54和CD86的上调。在树突状细胞中，细胞内γ干扰素表达峰值（通过荧光激活细胞分选显示）出现在第5天，比B细胞或巨噬细胞中的峰值表达早2天。这些发现表明，脾脏树突状细胞在体内疟疾感染的最早阶段就积极参与其中，并且可能在塑造随后的免疫反应中起关键作用。
