中文摘要：
耐碳青霉烯肺炎克雷伯菌（CRKP）可引发革兰氏阴性菌肺部感染及致死性肺炎脓毒症，目前临床可用治疗手段十分有限。肺组织密集分布着伤害感受器感觉神经元，这类神经元负责调控呼吸、咳嗽与支气管收缩功能。但伤害感受器在机体抵御革兰氏阴性肺部病原菌感染中的作用尚不明确。
本研究发现，肺支配型伤害感受器会促进耐碳青霉烯肺炎克雷伯菌所致肺炎及肺炎脓毒症的发生。在小鼠体内消融伤害感受器后，肺部对耐碳青霉烯肺炎克雷伯菌的清除能力显著增强，病菌跨肺泡扩散受到抑制，同时可有效避免小鼠出现低体温及死亡结局。
此外，消融伤害感受器能够促进中性粒细胞和 Ly6C⁺单核细胞募集，并上调细胞因子表达。在神经元消融小鼠模型中，耗竭 Ly6C⁺单核细胞会消除肺部及肺外组织对耐碳青霉烯肺炎克雷伯菌的清除效应，而耗竭中性粒细胞则无此作用，提示Ly6C⁺单核细胞是调控肺炎脓毒症的关键细胞群体。
进一步机制研究表明，神经肽降钙素基因相关肽可抑制 Ly6C⁺单核细胞中活性氧的生成，并削弱其对耐碳青霉烯肺炎克雷伯菌的杀菌能力。综上，靶向伤害感受器信号通路，有望成为治疗多重耐药革兰氏阴性菌感染及肺炎脓毒症的全新干预策略。
英文摘要：
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, 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.
论文信息：
论文题目：Lung-innervating nociceptor sensory neurons promote pneumonic sepsis during carbapenem-resistant Klebsiella pneumoniae lung infection
期刊名称：Science Advances
时间期卷：Vol 10, Issue 36(2024)
在线时间：2024年9月6日
DOI: 10.1126/sciadv.adl2267
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氯膦酸盐脂质体在细菌感染模型种清除肺脏肺泡巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Science Advances：肺伤害感受器感觉神经支配神经元，在耐碳青霉烯肺炎克雷伯菌肺部感染中促进肺炎性脓毒症发生。
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：
Depletion of AMs
Mice were first anesthetized with a 100 mg ketamine/kg body weight (Ketaset) and 10 mg xylazine/kg body weight (Rompun) cocktail, followed by intratracheal administration of single dose of 70 μl of CLLs (Liposoma) at 48 hours before infection. Control mice were administered with PBLs (70 μl per mouse) (Liposoma).
巨噬细胞清除材料和方法文献截图：
