中文摘要：
疟原虫可抑制宿主免疫应答以利于自身存活，但其背后的分子机制尚不明确。本研究发现，红内期疟原虫可显著诱导 CD4⁺Foxp3⁺CD25⁺调节性 T 细胞分泌可溶性纤维蛋白原样蛋白 2（sFGL2），该蛋白会大幅加重疟原虫感染程度。
机制层面，sFGL2 能够抑制巨噬细胞分泌单核细胞趋化蛋白 - 1（MCP-1），进而减少自然杀伤细胞 / 自然杀伤 T 细胞向脾脏募集，并下调干扰素 -γ 的生成。sFGL2 通过 FcγRIIB 受体依赖途径，抑制巨噬细胞 Toll 样受体 2 信号通路中 c-Jun 氨基末端激酶的磷酸化，从而阻断 MCP-1 释放。
值得注意的是，疟疾患者血清中 sFGL2 水平显著升高；体外实验证实，重组 FGL2 蛋白可显著抑制恶性疟原虫诱导巨噬细胞分泌 MCP-1。综上，本研究揭示了疟原虫一种全新的免疫逃逸策略，并阐明了 sFGL2 介导宿主固有免疫抑制的核心分子机制。
英文摘要：
Malaria parasites suppress host immune responses to facilitate their survival, but the underlying mechanism remains elusive. Here, we found that blood-stage malaria parasites predominantly induced CD4+Foxp3+CD25+ regulatory T cells to release soluble fibrinogen-like protein 2 (sFGL2), which substantially enhanced the infection. This was attributed to the capacity of sFGL2 to inhibit macrophages from releasing monocyte chemoattractant protein-1 (MCP-1) and to sequentially reduce the recruitment of natural killer/natural killer T cells to the spleen and the production of interferon-γ. sFGL2 inhibited c-Jun N-terminal kinase phosphorylation in the Toll-like receptor 2 signaling pathway of macrophages dependent on FcγRIIB receptor to release MCP-1. Notably, sFGL2 were markedly elevated in the sera of patients with malaria, and recombinant FGL2 substantially suppressed Plasmodium falciparum from inducing macrophages to release MCP-1. Therefore, we highlight a previously unrecognized immune suppression strategy of malaria parasites and uncover the fundamental mechanism of sFGL2 to suppress host innate immune responses.
论文信息：
论文题目：Blood-stage malaria parasites manipulate host innate immune responses through the induction of sFGL2
期刊名称：Science Advances
时间期卷：Vol 6, Issue9(2020)
在线时间：2020年2月26日
DOI: 10.1126/sciadv.aay9269
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes&Control Liposomes
办事处：靶点科技
Clodronate Liposomes氯膦酸盐脂质体静脉注射，清除疟原虫感染模型巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Science Advances：红内期疟原虫通过诱导可溶性纤维蛋白原样蛋白 2（sFGL2）调控宿主固有免疫应答.
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法：
In vivo macrophage depletion
For the depletion assay, 200 μg of the corresponding isotype control IgG, anti–IFN-γ mAb (clone XMG1.2, Bio X Cell), or anti–MCP-1 mAb (clone 2H5, Bio X Cell) was injected intraperitoneally into P. chabaudi–infected mice at −1, 0, 1, 3, and 5 days after infection. Depletion of NK/NKT cells was accomplished by intraperitoneal injection of 200 μg of anti-NK1.1 mAb (clone PK136, Bio X Cell) at −1, 0, 1, 3, and 5 days after infection. Depletion of Tregs was accomplished by intraperitoneal injection of 400 μg of anti-CD25 mAb (clone PC61.5, Bio X Cell) at −1, 0, 1, 3, 5, and 7 days after infection. Macrophage depletion in FGL2−/− mice was accomplished by intravenous injection of 200 μl of clodronate liposomes (Liposoma BV) on days −1, 2, and 5 of malaria parasite infection and with the injection of control liposomes (PBS) as a control. For rescue experiments, FGL2−/− mice received 25 μg of rFGL2 proteins (R&D Systems) by intravenous injection from the first day of infection until 5 days after infection.
巨噬细胞清除材料和方法文献截图：红内期疟原虫通过诱导可溶性纤维蛋白原样蛋白 2（sFGL2）调控宿主固有免疫应答。
