Bao Lam Q, Nhi Dang M, Huy Nguyen T, Kikuchi Mihoko, Yanagi Tetsuo, Hamano Shinjiro, Hirayama Kenji
Department of Immunogenetics, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Malar J. 2015 Jan 28;14:23. doi: 10.1186/s12936-014-0533-y.
Immunity to malaria requires innate, adaptive immune responses and Plasmodium-specific memory cells. Previously, mice semi-immune to malaria was developed. Three cycles of infection and cure ('three-cure') were required to protect mice against Plasmodium berghei (ANKA strain) infection.
C57BL/6 J mice underwent three cycles of P. berghei infection and drug-cure to become semi-immune. The spleens of infected semi-immune mice were collected for flow cytometry analysis. CD11c(+) cells of semi-immune mice were isolated and transferred into naïve mice which were subsequently challenged and followed up by survival and parasitaemia.
The percentages of splenic CD4(+) and CD11c(+) cells were increased in semi-immune mice on day 7 post-infection. The proportion and number of B220(+)CD11c(+)low cells (plasmacytoid dendritic cells, DCs) was higher in semi-immune, three-cure mice than in their naïve littermates on day 7 post-infection (2.6 vs 1.1% and 491,031 vs 149,699, respectively). In adoptive transfer experiment, three months after the third cured P. berghei infection, splenic CD11c(+) DCs of non-infected, semi-immune, three-cure mice slowed Plasmodium proliferation and decreased the death rate due to neurological pathology in recipient mice. In addition, anti-P. berghei IgG1 level was higher in mice transferred with CD11c(+) cells of semi-immune, three-cure mice than mice transferred with CD11c(+) cells of naïve counterparts.
CD11c(+) cells of semi-immune mice protect against experimental cerebral malaria three months after the third cured malaria, potentially through protective plasmacytoid DCs and enhanced production of malaria-specific antibody.
对疟疾的免疫需要先天性、适应性免疫反应以及疟原虫特异性记忆细胞。此前，已培育出对疟疾具有半免疫能力的小鼠。需要三个感染和治愈周期（“三治愈”）来保护小鼠免受伯氏疟原虫（ANKA株）感染。
C57BL/6 J小鼠接受三个周期的伯氏疟原虫感染和药物治愈以获得半免疫能力。收集感染的半免疫小鼠的脾脏用于流式细胞术分析。分离半免疫小鼠的CD11c(+)细胞并转移到未感染的小鼠中，随后对这些小鼠进行攻击，并通过存活率和寄生虫血症进行随访。
感染后第7天，半免疫小鼠脾脏中CD4(+)和CD11c(+)细胞的百分比增加。感染后第7天，半免疫的“三治愈”小鼠中B220(+)CD11c(+)低细胞（浆细胞样树突状细胞，DCs）的比例和数量高于其未感染的同窝小鼠（分别为2.6%对1.1%和491,031对149,699）。在过继转移实验中，第三次治愈伯氏疟原虫感染三个月后，未感染的半免疫“三治愈”小鼠的脾脏CD11c(+) DCs减缓了疟原虫的增殖，并降低了受体小鼠因神经病理学导致的死亡率。此外，用半免疫“三治愈”小鼠的CD11c(+)细胞转移的小鼠中抗伯氏疟原虫IgG1水平高于用未感染同窝小鼠的CD11c(+)细胞转移的小鼠。
半免疫小鼠的CD11c(+)细胞在第三次治愈疟疾三个月后可预防实验性脑型疟疾，可能是通过保护性浆细胞样DCs和增强疟疾特异性抗体的产生。
