State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, P.R. China; School of Life Sciences, University of Science and Technology of China, Hefei, P.R. China.
Eur J Immunol. 2013 Nov;43(11):2907-18. doi: 10.1002/eji.201343512. Epub 2013 Aug 27.
Cerebral malaria (CM) is a neurological syndrome often occurring in severe malaria. Although CM is known as an immunopathology in brain tissue mediated by excessive proinflammatory cytokines, the immunoregulatory mechanism is poorly understood. Here, we investigated the role of IL-10-producing regulatory B (Breg) cells in modulating CM development in a murine model of Plasmodium berghei ANKA infection. We observed that blood-stage P. berghei induced expansion of IL-10-producing Breg cells in C57BL/6 mice. Adoptive transfer of IL-10(+) Breg cells to P. berghei infected mice significantly reduced the accumulation of NK and CD8(+) T cells and hemorrhage in brain tissue, and improved the survival of the mice compared with control groups, although parasitemia levels were not altered. Treatment of Breg-cell recipient mice with anti-IL-10 receptor mAb blocked the protective effect of Breg cells. Adoptive transfer of CD4(+) CD25(+) Treg cells failed to prevent CM in infected mice. Spleen cells from Breg-cell recipient mice produced increased levels of IL-10 in vitro. Cell co-culture showed that purified IL-10(+) B cells, but not IL-10(-) B cells, promoted IL-10 production by CD4(+) T cells. These results demonstrate that IL-10-producing Breg cells may represent an important mechanism for controlling the immunopathology and prevention of CM associated with P. berghei infection.
脑型疟疾（CM）是一种常发生于严重疟疾的神经综合征。尽管 CM 被认为是脑组织中由过度促炎细胞因子介导的免疫病理学，但免疫调节机制仍知之甚少。在这里，我们在伯氏疟原虫 ANKA 感染的小鼠模型中研究了产生白细胞介素 10 的调节性 B（Breg）细胞在调节 CM 发展中的作用。我们观察到，血期疟原虫诱导 C57BL/6 小鼠中产生白细胞介素 10 的 Breg 细胞扩增。与对照组相比，将 IL-10(+)Breg 细胞过继转移到感染伯氏疟原虫的小鼠中，显著减少了 NK 和 CD8(+)T 细胞在脑组织中的积累和出血，并提高了小鼠的存活率，尽管寄生虫血症水平没有改变。用抗白细胞介素 10 受体 mAb 治疗 Breg 细胞受者小鼠可阻断 Breg 细胞的保护作用。过继转移 CD4(+)CD25(+)Treg 细胞不能预防感染小鼠的 CM。从 Breg 细胞受者小鼠的脾细胞中体外产生增加水平的白细胞介素 10。细胞共培养表明，纯化的 IL-10(+)B 细胞，但不是 IL-10(-)B 细胞，可促进 CD4(+)T 细胞产生白细胞介素 10。这些结果表明，产生白细胞介素 10 的 Breg 细胞可能是控制与伯氏疟原虫感染相关的免疫病理学和预防 CM 的重要机制。
