Interaction of mouse dendritic cells and malaria-infected erythrocytes: Uptake, maturation, and antigen presentation
Interaction of mouse dendritic cells and malaria-infected erythrocytes: Uptake, maturation, and antigen presentation
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DOI：
10.4049/jimmunol.176.1.441
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发表时间：
2006-01-01
影响因子：
4.4
通讯作者：
Stevenson, MM
中科院分区：
文献类型：
--
作者：
Ing, R;Segura, M;Stevenson, MM
与它们在检测感染中的精液作用一致，小鼠骨髓来源的和脾CD 11 c（+）树突状细胞（DC）都表现出比未感染的RBC（nRBC）更高水平的对疟原虫chabaudi寄生的RBC（pRBC）的摄取，这是通过我们新开发的流式细胞术技术确定的，该技术在与DC共培养之前使用染料CFSE标记RBC。为了证实与CFSE标记的pRBC共培养后CD 11 c（+）细胞表达CFSE代表DC内化pRBC，我们通过共聚焦荧光显微镜显示CFSE标记的pRBC和PE标记的CD 11 c（+）DC共定位。用细胞松弛素D处理DC显着抑制pRBC的摄取，表明摄取是一个肌动蛋白依赖性吞噬过程。体内感染后脾CD 11 c（+）DCs对pRBC的摄取显著增强，并与诱导DC成熟、IL-12产生、刺激CD 4（+）T细胞增殖和IFN-γ产生相关。这些结果表明，DC选择性吞噬pRBC并将pRBC衍生的Ag呈递给CD 4（+）T细胞，从而促进对血液期疟疾感染的保护性Th 1依赖性免疫应答的发展。
Consistent with their seminal role in detecting infection, both mouse bone marrow-derived and splenic CD11c(+) dendritic cells (DCs) exhibited higher levels of uptake of Plasmodium chabaudi-parasitized RBCs (pRBCs) than of noninfected RBCs (nRBCs) as determined by our newly developed flow cytometric technique using the dye CFSE to label RBCs before coculture with DCs. To confirm that expression of CFSE by CD11c(+) cells following coculture with CFSE-labeled pRBCs represents internalization of pRBC by DCs, we showed colocalization of CFSE-labeled pRBCs and PE-labeled CD11c(+) DCs by confocal fluorescence microscopy. Treatment of DCs with cytochalasin D significantly inhibited the uptake of pRBCs, demonstrating that uptake is an actin-dependent phagocytic process. The uptake of pRBCs by splenic CD11c(+) DCs was significantly enhanced after infection in vivo and was associated with the induction of DC maturation, IL-12 production, and stimulation of CD4(+) T cell proliferation and IFN-gamma production. These results suggest that DCs selectively phagocytose pRBCs and present pRBC-derived Ags to CD4(+) T cells, thereby promoting development of protective Th1-dependent immune responses to blood-stage malaria infection.