Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, 14476 Potsdam, Germany.
J Immunol. 2013 Sep 1;191(5):2551-9. doi: 10.4049/jimmunol.1203451. Epub 2013 Aug 5.
Cerebral malaria (CM) is the most severe complication of malaria. The murine Plasmodium berghei ANKA (PbA) infection model has helped to identify crucial players in the pathogenesis of CM. However, the role of pattern recognition receptors in innate immunity to CM induction is still poorly understood. C-type lectin receptors (CLRs) represent a family of pattern recognition receptors that recognize carbohydrate structures on pathogens and self-Ags often in a Ca(2+)-dependent manner. In this study, we investigated the role of the CLR dendritic cell immunoreceptor (DCIR) in the genesis of CM. Using the murine PbA infection, we show in this article that DCIR is essential for the development of CM. Although PbA infection led to 80% CM in wild-type C57BL/6 mice, DCIR-deficient mice were highly protected with only 15% CM development. In accordance with the reduced CM incidence in DCIR(-/-) mice, CD8(+) T cell sequestration was markedly reduced in brains of PbA-infected DCIR(-/-) mice, which was accompanied by reduced brain inflammation. Reduced T cell sequestration in the brain was caused by decreased TNF-α levels in sera, as well as a modulated activation of CD4(+) and CD8(+) T cells in spleen of PbA-infected DCIR(-/-) mice. This study indicates that DCIR is critically involved in CM induction, thus highlighting the importance of this CLR in innate immunity during malaria infection.
脑型疟疾（CM）是疟疾最严重的并发症。鼠疟原虫 Plasmodium berghei ANKA（PbA）感染模型有助于确定 CM 发病机制中的关键因素。然而，模式识别受体在固有免疫诱导 CM 中的作用仍知之甚少。C 型凝集素受体（CLRs）是一组识别病原体和自身抗原上碳水化合物结构的模式识别受体，通常以 Ca(2+)依赖性方式识别。在这项研究中，我们研究了 CLR 树突状细胞免疫受体（DCIR）在 CM 发生中的作用。使用鼠疟原虫 PbA 感染，我们在本文中表明 DCIR 对 CM 的发生至关重要。尽管 PbA 感染导致野生型 C57BL/6 小鼠 80%发生 CM，但 DCIR 缺陷型小鼠的发病率非常低，仅为 15%。与 DCIR(-/-) 小鼠 CM 发生率降低相一致的是，PbA 感染的 DCIR(-/-) 小鼠脑内 CD8(+) T 细胞的栓塞明显减少，伴随脑炎症减轻。大脑中 T 细胞栓塞减少是由于血清中 TNF-α 水平降低，以及 PbA 感染的 DCIR(-/-) 小鼠脾中 CD4(+)和 CD8(+) T 细胞的激活受到调节所致。这项研究表明，DCIR 对 CM 的诱导起着至关重要的作用，从而突出了这种 CLR 在疟疾感染固有免疫中的重要性。
