品牌：Liposoma

产地：荷兰

货号：CP-005-005

规格：5ml+5ml

品名：Clodronateliposomes & Control Liposomes

代理：靶点科技

部位：肺脏

细胞：肺泡巨噬细胞（AM）

剂量：70ul

方式：滴鼻（intratracheal administration）

时间点：建模前48h

题目：Lung-innervating nociceptor sensory neurons promote pneumonic sepsis during carbapenem-resistant Klebsiella pneumoniae lung infection

期刊：SCIENCE ADVANCES

时间：6 Sep 2024

期卷：Vol 10, Issue 36

链接：DOI: 10.1126/sciadv.adl6162

摘要：

耐碳青霉烯类肺炎克雷伯菌 （CRKP） 会导致革兰氏阴性的肺部感染和致命的肺炎脓毒症，这些疾病的治疗选择有限。肺部由介导呼吸、咳嗽和支气管收缩的伤害感受器感觉神经元密集支配。伤害感受器在防御革兰氏阴性肺病原体中的作用尚不清楚。在这里，我们发现肺支配伤害感受器促进 CRKP 肺炎和肺脓毒症。小鼠伤害感受器消融可增加肺 CRKP 清除率，抑制 CRKP 的经肺泡播散，并保护小鼠免受体温过低和死亡。此外，伤害感受器的消融增强了中性粒细胞和 Ly6Chi 单核细胞的募集以及细胞因子诱导。巨噬细胞清除剂Clodronate Liposomes（liposoma，CP-005-005）清除耗竭小鼠中 Ly6Chi 单核细胞的耗竭而不是中性粒细胞的耗竭，肺和肺外 CRKP 清除率降低，表明 Ly6Chi 单核细胞是调节肺脓毒症的关键细胞群。此外，神经肽降钙素基因相关肽抑制 Ly6Chi 单核细胞中活性氧的诱导及其 CRKP 杀伤能力。靶向伤害感受器信号传导可能是治疗多重耐药革兰氏阴性菌感染和肺炎脓毒症的治疗方法。

Abstract:

Carbapenem-resistant Klebsiella pneumoniae (CRKP) causes Gram-negative lung infections and fatal pneumonic sepsis for which limited therapeutic options are available. The lungs are densely innervated by nociceptor sensory neurons that mediate breathing, cough, and bronchoconstriction. The role of nociceptors in defense against Gram-negative lung pathogens is unknown. Here, we found that lung-innervating nociceptors promote CRKP pneumonia and pneumonic sepsis. Ablation of nociceptors in mice increased lung CRKP clearance, suppressed trans-alveolar dissemination of CRKP, and protected mice from hypothermia and death. Furthermore, ablation of nociceptors enhanced the recruitment of neutrophils and Ly6Chi monocytes and cytokine induction. Depletion of Ly6Chi monocytes（liposoma，CP-005-005）, but not of neutrophils, abrogated lung and extrapulmonary CRKP clearance in ablated mice, suggesting that Ly6Chi monocytes are a critical cellular population to regulate pneumonic sepsis. Further, neuropeptide calcitonin gene–related peptide suppressed the induction of reactive oxygen species in Ly6Chi monocytes and their CRKP-killing abilities. Targeting nociceptor signaling could be a therapeutic approach for treating multidrug-resistant Gram-negative infection and pneumonic sepsis.

Liposoma巨噬细胞清除剂氯膦酸二钠脂质体清除肺泡巨噬细胞AM：