中文摘要：

抗微生物抵抗力的上升导致对评估噬菌体疗法的新兴趣。在小鼠模型中，针对铜绿假单胞菌引起的急性肺炎的高效治疗依赖于噬菌体与中性粒细胞的协同抗菌活性。在这里，我们展示了荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes清除肺泡巨噬细胞（AM）缩短成年雄性小鼠的生存时间，但并未提高肺中铜绿假单胞菌的负荷。令人意外的是，在接受噬菌体治疗后，AM清除的小鼠的肺中铜绿假单胞菌水平显著低于免疫能力正常的小鼠。为了探讨治疗小鼠中AM缺失益处的潜在机制，我们开发了一个关于噬菌体、细菌和先天免疫系统动态的数学模型。根据数据拟合的模型的模拟结果表明，AM减少了肺中的噬菌体密度。我们实验确认，在免疫能力正常的小鼠中，噬菌体在体内衰减的速度比AM缺失的动物快，且AM能够吞噬治疗性噬菌体。这些发现表明噬菌体、细菌与免疫系统之间的反馈作用在临床环境中影响噬菌体疗法的结果。

英文摘要：

The rise of antimicrobial resistance leads to renewed interest in evaluating phage therapy. In murine models highly effective treatment of acute pneumonia caused by Pseudomonas aeruginosa relies on the synergistic antibacterial activity of bacteriophages with neutrophils. Here, we show that depletion of alveolar macrophages (AM) shortens the survival of adult male mice without boosting the P. aeruginosa load in the lungs. Unexpectedly, upon bacteriophage treatment, pulmonary levels of P. aeruginosa are significantly lower in AM-depleted than in immunocompetent mice. To explore potential mechanisms underlying the benefit of AM-depletion in treated mice, we develop a mathematical model of bacteriophage, bacteria, and innate immune system dynamics. Simulations from the model fitted to data suggest that AM reduce bacteriophage density in the lungs. We experimentally confirm that the in vivo decay of bacteriophage is faster in immunocompetent compared to AM-depleted animals and that AM phagocytize therapeutic bacteriophage. These findings demonstrate the involvement of feedback between bacteriophage, bacteria, and the immune system in shaping the outcomes of phage therapy in clinical settings.

论文信息：

论文题目：Macrophage-induced reduction of bacteriophage density limits the efficacy of in vivo pulmonary phage therapy

期刊名称：Nature Communications

时间期卷：16, Article number: 5725 (2025)

在线时间：2025年7月1日

DOI：doi.org/10.1038/s41467-025-61268-1

产品信息：

货号：CP-005-005

规格：5ml+5ml

品牌：Liposoma

产地：荷兰

名称：Clodronate Liposomes and Control Liposomes

办事处：Target Technology(靶点科技)

Clodronate Liposomes氯膦酸盐脂质体清除肺泡巨噬细胞（AM），在细菌感染的炎性模型中单核巨噬细胞功能研究，荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications：巨噬细胞引起的噬菌体密度降低限制了体内肺部噬菌体治疗的效果

Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法：

Macrophage depletion

AM depletion was obtained by the intra-tracheal administration a single dose of 400?µg of clodronate liposomes or empty liposomes (LIPOSOMA, city), four days prior infection. For the intra-tracheal administration, the mice were anesthetized by intraperitoneal injection of a mixture of two vol of ketamine (10?mg/mL) and one vol of xylazine (1?mg/mL) in a solution of NaCl 0.9%. The dose administrated to each mouse was adjusted to 0.01?mg of the ketamine-xylazine mixture per 1?g of body mass.　　

材料和方法文献截图：