中文摘要：
单核细胞增生李斯特菌 （LM） 具有突破多重屏障并引发复杂免疫反应的能力。然而，关于 LM 如何逃避体内的先天免疫监视，仍然缺乏明确的理解。在这里，我们利用肝脏活体成像来阐明肝脏感染期间 LM 的动态过程。我们发现 LM 可以通过李斯特菌溶血素 O （LLO） 迅速从库普弗细胞 （KCs） 中逃逸并在肝细胞内增殖。LM 暴露于肝窦后，中性粒细胞在感染部位迅速聚集。随后，LM 可以主要在脾脏中诱导 I 型干扰素 （IFN-I） 的产生，脾脏中干扰素全身作用于中性粒细胞，通过使 ERK 通路失活来阻碍其蜂群，从而逃避中性粒细胞介导的去除。此外，我们的研究结果表明，病毒诱导的 IFN-I 抑制中性粒细胞蜂拥，新冠 患者表现出中性粒细胞聚集功能受损。总之，我们的研究结果提供了令人信服的证据，证明以 LM 为代表的细胞内细菌可以劫持宿主对病毒感染的防御机制以逃避免疫监视。此外，由 IFN-I 引起的中性粒细胞聚集受损是导致病毒感染后细菌感染易感性增加的重要因素之一。
英文摘要：
Listeria monocytogenes (LM) possesses the ability to breach multiple barriers and elicit intricate immune responses. However, there remains a lack of explicit understanding regarding how LM evades innate immune surveillance within the body. Here, we utilized liver intravital imaging to elucidate the dynamic process of LM during infection in the liver. We discovered that LM can rapidly escape from Kupffer cells (KCs) through listeriolysin O (LLO) and proliferate within hepatocytes. Upon LM exposure to the hepatic sinusoids, neutrophils rapidly aggregate at the site of infection. Subsequently, LM can induce type I interferon (IFN-I) production primarily in the spleen, which acts systemically on neutrophils to hamper their swarming by deactivating the ERK pathway, thus evading neutrophil-mediated eradication. Furthermore, our findings suggest that virus-induced IFN-I suppresses neutrophil swarming, and patients exhibit impaired neutrophil aggregation function. In conclusion, our findings provide compelling evidence demonstrating that intracellular bacteria represented by LM can hijack host defense mechanisms against viral infections to evade immune surveillance. Additionally, impaired neutrophil swarming caused by IFN-I is one of the significant factors contributing to the increased susceptibility to bacterial infections following viral infections.
论文信息：
论文题目：Inhibition of neutrophil swarming by type I interferon promotes intracellular bacterial evasion
期刊名称：Nature Communications
时间期卷：15, Article number: 8663 (2024)
在线时间：2024年10月7日
DOI：doi.org/10.1038/s41467-024-53060-4
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）
氯膦酸盐脂质体清除肝脏巨噬细胞，肝脏定居巨噬细胞KF是李斯特菌 （LM）的主要宿主。李斯特菌 （LM）从肝脏巨噬细胞逃逸就迅速在肝细胞中复制。氯膦酸盐二钠脂质体清除巨噬细胞在李斯特菌（LM）感染模型中性粒细胞功能研究，荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications：I 型干扰素抑制中性粒细胞蜂拥促进细胞内细菌逃逸
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法：
splenectomized (SpX) mice exhibited increased resistance to LM infection。脾切除 （SpX） 小鼠对 LM 感染的抵抗力增加。使用Lipsoma巨噬细胞细胞清除剂Clodronateliposomes（CLL）。剂量是100ul，李斯特菌感染后2h注射。注射的剂量和时间点仅仅参考文献。具体需要以自己的实验目的为准。比如为什么是100ul？为什么是感染后2h注射？
Sham-or Spx-treated Mice were administered with Clodronateliposomes (CKLL，100μL) at 2h after LM infection. (a) Representative intravital images depicting the LM load in the liver at 48h post-infection with 1×106CFU LM-GFP. Scale bar, 200 μm. (b) Bacterial load in the liver was assessed at 48h post-infection with 1×106CFU LM-GFP. Data from 3 mice in each group。
a WT mice were intravenously infected with 1 × 108 CFU of LM-GFP. The bacterial load in the liver, spleen, lung, and kidney was assessed 30 min post-infection. Data were from three mice. (P < 0.0001). b Intravital images showing the capture of LM in the liver. APC anti-F4/80-labeled KCs (blue) and LM-GFP (green). Captured LM are indicated by yellow arrows. Scale bar, 50 μm. c–e Mice were infected with 1 × 108 CFU of the indicated LM strains intravenously. Dynamic intravital images showing the escape of LM-GFP (c), LM-ΔactA-GFP (d), and LM-Δhly-GFP (e) from KCs. APC anti-F4/80-labeled KCs (blue), bacteria (green), and nucleic acid staining dye PI (red) are shown. Escaped LM are indicated by yellow arrows.
