人源化小鼠用于研究持續(xù)的惡性瘧原蟲血液階段感染和傳播

中文摘要：

惡性瘧原蟲是人類廣泛的瘧疾寄生蟲。由于存在血管外的儲(chǔ)存庫以及從休眠肝臟階段復(fù)發(fā)的感染，惡性瘧原蟲特別難以控制和消除。實(shí)驗(yàn)研究受到限制，因?yàn)闊o法體外維持惡性瘧原蟲的培養(yǎng)，這是由于它對(duì)未成熟紅細(xì)胞的趨向。在這里，我們描述了一種新的類人小鼠模型，它能夠支持有效的人類紅細(xì)胞生成并維持接種的冷凍保存惡性瘧原蟲的持久增殖及其性別分化，包括在骨髓中。成熟性配子被傳遞到按蚊中，從而形成唾液腺孢子蟲。重要的是，在二次轉(zhuǎn)移新鮮或冷凍感染的骨髓細(xì)胞到未感染的嵌合體后，血液階段的惡性瘧原蟲得以維持。該模型提供了一個(gè)新的工具，以體內(nèi)方式研究紅細(xì)胞內(nèi)惡性瘧原蟲的生物學(xué)。

英文摘要：

Plasmodium vivax is the most widespread human malaria parasite. Due to the presence of extravascular reservoirs and relapsing infections from dormant liver stages, P. vivax is particularly difficult to control and eliminate. Experimental research is hampered by the inability to maintain P. vivax cultures in vitro, due to its tropism for immature red blood cells (RBCs). Here, we describe a new humanized mice model that can support efficient human erythropoiesis and maintain long-lasting multiplication of inoculated cryopreserved P. vivax parasites and their sexual differentiation, including in bone marrow. Mature gametocytes were transmitted to Anopheles mosquitoes, which led to the formation of salivary gland sporozoites. Importantly, blood-stage P. vivax parasites were maintained after the secondary transfer of fresh or frozen infected bone marrow cells to na?ve chimeras. This model provides a unique tool for investigating, in vivo, the biology of intraerythrocytic P. vivax.

論文信息：

論文題目：Humanized mice for investigating sustained Plasmodium vivax blood-stage infections and transmission

期刊名稱：Nature Communications

時(shí)間期卷：13, Article number: 4123 (2022)

在線時(shí)間：2022年7月15日

DOI：doi.org/10.1038/s41467-022-31864-6

產(chǎn)品信息：

貨號(hào)：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes and Control Liposomes

辦事處：Target Technology(靶點(diǎn)科技)

氯膦酸鹽脂質(zhì)體清除單核巨噬細(xì)胞，在人源化小鼠模型瘧原蟲誘導(dǎo)的炎性模型中單核巨噬細(xì)胞功能研究，荷蘭Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見刊于Nature Communications：人源化小鼠用于研究持續(xù)的惡性瘧原蟲血液階段感染和傳播。

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法：

HIS-HEry mouse infection with P. vivax

P. vivax isolates were thawed with a stepwise NaCl method, as previously described33, and washed in PBS. Before being used to infect mice, the isolates were tested for Plasmodium parasitemia by examining thick PB smears with Giemsa staining. Next, RBC pellets of the isolates were resuspended in PBS at a concentration of 2.5.106 to 5.106 parasitized RBCs per ml. One day before infection, 12- to 20-week-old HIS-HEry chimeras received intravenous injections of 200?μl liposome clodronate (Liposoma BV, The Netherlands). This injection was repeated every 5 days for the duration of the experiments. HIS-HEry mice were infected intravenously, under anesthesia, with 106?5.106 infected RBCs from either a single isolate (Pv1, Pv2, Pv3, or Pv4) or a mixture of three isolates (Pv5), except when stated otherwise in figure legends. Then, BM and blood were collected from euthanized mice on days 1, 7, 14, or 21 after infection. To collect BM, the two femurs, tibias, and humeri were dissected, the bones were crushed, and cell suspensions were filtered through 40-μM filters before processing. Each experiment was conducted with chimeras engrafted with CD34+ cells from the same CB donor.

材料和方法文獻(xiàn)截圖：