中文摘要：

循環(huán)型 Ly6C 高表達（Ly6C^hi）單核細胞在其抗菌效應(yīng)功能耗竭后通常會發(fā)生細胞死亡，這一現(xiàn)象限制了其后續(xù)分化為巨噬細胞的能力。這也使得我們難以闡明：宿主在細菌入侵過程中，如何高效補充組織原位巨噬細胞儲備池，以避免感染引發(fā)的機體損傷。本研究證實，增殖型過渡前單核細胞（TpMo）作為成熟 Ly6C 高表達單核細胞（MatMo）的直接前體細胞，會在急性細菌感染與膿毒癥刺激下動員至外周循環(huán)。成熟單核細胞易受細菌誘導(dǎo)發(fā)生細胞凋亡，而過渡前單核細胞凋亡敏感性更低，是此時巨噬細胞補充的主要來源。此外，過渡前單核細胞及其分化產(chǎn)生的巨噬細胞可通過制衡成熟單核細胞介導(dǎo)的促炎細胞因子應(yīng)答，參與機體免疫防御。相應(yīng)地，過繼回輸過渡前單核細胞能夠提升致死性膿毒癥模型的存活率。綜上，本研究揭示了過渡前單核細胞在細菌感染中發(fā)揮保護作用，同時參與塑造單核細胞源性巨噬細胞的異質(zhì)性，進而造成不同的疾病預(yù)后。

英文摘要：

Circulating Ly6C^hi monocytes often undergo cellular death upon exhaustion of their antibacterial effector functions, which limits their capacity for subsequent macrophage differentiation. This shrouds the understanding on how the host replaces the tissue-resident macrophage niche effectively during bacterial invasion to avert infection morbidity. Here, we show that proliferating transitional premonocytes (TpMos), an immediate precursor of mature Ly6C^hi monocytes (MatMos), were mobilized into the periphery in response to acute bacterial infection and sepsis. TpMos were less susceptible to apoptosis and served as the main source of macrophage replenishment when MatMos were vulnerable toward bacteria-induced cellular death. Furthermore, TpMo and its derived macrophages contributed to host defense by balancing the proinflammatory cytokine response of MatMos. Consequently, adoptive transfer of TpMos improved the survival outcome of lethal sepsis. Our findings hence highlight a protective role for TpMos during bacterial infections and their contribution toward monocyte-derived macrophage heterogeneity in distinct disease outcomes.

論文信息：

論文題目：Transitional premonocytes emerge in the periphery for host defense against bacterial infections

期刊名稱：Science Advances

時間期卷：Vol 8, Issue9(2022)

在線時間：2022年3月4日

DOI: 10.1126/sciadv.abj46

產(chǎn)品信息：

貨號：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes&Control Liposomes

辦事處：靶點科技

Clodronate Liposomes氯膦酸鹽脂質(zhì)體腹腔注射，清除細菌感染模型里巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Science Advances：過渡型前單核細胞在外周組織中產(chǎn)生，參與宿主抵御細菌感染的免疫防御。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除巨噬細胞的材料和方法：

In vivo macrophage depletion

Clodronate liposomes suspension (LIPOSOMA) was administered intraperitoneally according to the recommended doses (100 μl of suspension/10 g of mouse weight), and E. coli infection was carried out 66 hours after. PBS liposomes suspension was injected as a control. Macrophages were depleted without affecting blood monocytes as previously described.

按照推薦給藥劑量（每 10 克小鼠體重注射 100 微升混懸液）對小鼠腹腔注射氯膦酸二鈉脂質(zhì)體混懸液（品牌：LIPOSOMA），66 小時后開展大腸桿菌感染造模；同步注射 PBS 空白脂質(zhì)體混懸液作為對照組。如前人報道所述，該處理方案可特異性耗竭巨噬細胞，且不影響外周血單核細胞數(shù)量。

巨噬細胞清除材料和方法文獻截圖：過渡型前單核細胞在外周組織中產(chǎn)生，參與宿主抵御細菌感染的免疫防御。