中文摘要:
瘧原蟲可抑制宿主免疫應答以利于自身存活,但其背后的分子機制尚不明確。本研究發現,紅內期瘧原蟲可顯著誘導 CD4?Foxp3?CD25?調節性 T 細胞分泌可溶性纖維蛋白原樣蛋白 2(sFGL2),該蛋白會大幅加重瘧原蟲感染程度。
機制層面,sFGL2 能夠抑制巨噬細胞分泌單核細胞趨化蛋白 - 1(MCP-1),進而減少自然殺傷細胞 / 自然殺傷 T 細胞向脾臟募集,并下調干擾素 -γ 的生成。sFGL2 通過 FcγRIIB 受體依賴途徑,抑制巨噬細胞 Toll 樣受體 2 信號通路中 c-Jun 氨基末端激酶的磷酸化,從而阻斷 MCP-1 釋放。
值得注意的是,瘧疾患者血清中 sFGL2 水平顯著升高;體外實驗證實,重組 FGL2 蛋白可顯著抑制惡性瘧原蟲誘導巨噬細胞分泌 MCP-1。綜上,本研究揭示了瘧原蟲一種全新的免疫逃逸策略,并闡明了 sFGL2 介導宿主固有免疫抑制的核心分子機制。
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.
論文信息:
論文題目:Blood-stage malaria parasites manipulate host innate immune responses through the induction of sFGL2
期刊名稱:Science Advances
時間期卷:Vol 6, Issue9(2020)
在線時間:2020年2月26日
DOI: 10.1126/sciadv.aay9269
產品信息:
貨號:CP-005-005
規格:5ml+5ml
品牌:Liposoma
產地:荷蘭
名稱:Clodronate Liposomes&Control Liposomes
辦事處:靶點科技
Clodronate Liposomes氯膦酸鹽脂質體靜脈注射,清除瘧原蟲感染模型巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Science Advances:紅內期瘧原蟲通過誘導可溶性纖維蛋白原樣蛋白 2(sFGL2)調控宿主固有免疫應答.

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體清除巨噬細胞的材料和方法:
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.
巨噬細胞清除材料和方法文獻截圖:紅內期瘧原蟲通過誘導可溶性纖維蛋白原樣蛋白 2(sFGL2)調控宿主固有免疫應答。

請輸入賬號
請輸入密碼
請輸驗證碼
以上信息由企業自行提供,信息內容的真實性、準確性和合法性由相關企業負責,化工儀器網對此不承擔任何保證責任。
溫馨提示:為規避購買風險,建議您在購買產品前務必確認供應商資質及產品質量。