过渡型前单核细胞在外周组织中产生，参与宿主抵御细菌感染的免疫防御。

中文摘要：

循环型 Ly6C 高表达（Ly6C^hi）单核细胞在其抗菌效应功能耗竭后通常会发生细胞死亡，这一现象限制了其后续分化为巨噬细胞的能力。这也使得我们难以阐明：宿主在细菌入侵过程中，如何高效补充组织原位巨噬细胞储备池，以避免感染引发的机体损伤。本研究证实，增殖型过渡前单核细胞（TpMo）作为成熟 Ly6C 高表达单核细胞（MatMo）的直接前体细胞，会在急性细菌感染与脓毒症刺激下动员至外周循环。成熟单核细胞易受细菌诱导发生细胞凋亡，而过渡前单核细胞凋亡敏感性更低，是此时巨噬细胞补充的主要来源。此外，过渡前单核细胞及其分化产生的巨噬细胞可通过制衡成熟单核细胞介导的促炎细胞因子应答，参与机体免疫防御。相应地，过继回输过渡前单核细胞能够提升致死性脓毒症模型的存活率。综上，本研究揭示了过渡前单核细胞在细菌感染中发挥保护作用，同时参与塑造单核细胞源性巨噬细胞的异质性，进而造成不同的疾病预后。

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.

论文信息：

论文题目：Transitional premonocytes emerge in the periphery for host defense against bacterial infections

期刊名称：Science Advances

时间期卷：Vol 8, Issue9(2022)

在线时间：2022年3月4日

DOI: 10.1126/sciadv.abj46

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氯膦酸盐脂质体腹腔注射，清除细菌感染模型里巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Science Advances：过渡型前单核细胞在外周组织中产生，参与宿主抵御细菌感染的免疫防御。

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

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.

按照推荐给药剂量（每 10 克小鼠体重注射 100 微升混悬液）对小鼠腹腔注射氯膦酸二钠脂质体混悬液（品牌：LIPOSOMA），66 小时后开展大肠杆菌感染造模；同步注射 PBS 空白脂质体混悬液作为对照组。如前人报道所述，该处理方案可特异性耗竭巨噬细胞，且不影响外周血单核细胞数量。

巨噬细胞清除材料和方法文献截图：过渡型前单核细胞在外周组织中产生，参与宿主抵御细菌感染的免疫防御。