I 型干擾素抑制中性粒細(xì)胞蜂擁促進(jìn)細(xì)胞內(nèi)細(xì)菌逃逸

中文摘要：

單核細(xì)胞增生李斯特菌 （LM） 具有突破多重屏障并引發(fā)復(fù)雜免疫反應(yīng)的能力。然而，關(guān)于 LM 如何逃避體內(nèi)的先天免疫監(jiān)視，仍然缺乏明確的理解。在這里，我們利用肝臟活體成像來闡明肝臟感染期間 LM 的動態(tài)過程。我們發(fā)現(xiàn) LM 可以通過李斯特菌溶血素 O （LLO） 迅速從庫普弗細(xì)胞 （KCs） 中逃逸并在肝細(xì)胞內(nèi)增殖。LM 暴露于肝竇后，中性粒細(xì)胞在感染部位迅速聚集。隨后，LM 可以主要在脾臟中誘導(dǎo) I 型干擾素 （IFN-I） 的產(chǎn)生，脾臟中干擾素全身作用于中性粒細(xì)胞，通過使 ERK 通路失活來阻礙其蜂群，從而逃避中性粒細(xì)胞介導(dǎo)的去除。此外，我們的研究結(jié)果表明，病毒誘導(dǎo)的 IFN-I 抑制中性粒細(xì)胞蜂擁，新冠 患者表現(xiàn)出中性粒細(xì)胞聚集功能受損。總之，我們的研究結(jié)果提供了令人信服的證據(jù)，證明以 LM 為代表的細(xì)胞內(nèi)細(xì)菌可以劫持宿主對病毒感染的防御機制以逃避免疫監(jiān)視。此外，由 IFN-I 引起的中性粒細(xì)胞聚集受損是導(dǎo)致病毒感染后細(xì)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.

論文信息：

論文題目：Inhibition of neutrophil swarming by type I interferon promotes intracellular bacterial evasion

期刊名稱：Nature Communications

時間期卷：15, Article number: 8663 (2024)

在線時間：2024年10月7日

DOI：doi.org/10.1038/s41467-024-53060-4

產(chǎn)品信息：

貨號：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes and Control Liposomes

辦事處：Target Technology（靶點科技）

氯膦酸鹽脂質(zhì)體清除肝臟巨噬細(xì)胞，肝臟定居巨噬細(xì)胞KF是李斯特菌 （LM）的主要宿主。李斯特菌 （LM）從肝臟巨噬細(xì)胞逃逸就迅速在肝細(xì)胞中復(fù)制。氯膦酸鹽二鈉脂質(zhì)體清除巨噬細(xì)胞在李斯特菌（LM）感染模型中性粒細(xì)胞功能研究，荷蘭Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見刊于Nature Communications：I 型干擾素抑制中性粒細(xì)胞蜂擁促進(jìn)細(xì)胞內(nèi)細(xì)菌逃逸

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體的材料和方法：

splenectomized (SpX) mice exhibited increased resistance to LM infection。脾切除 （SpX） 小鼠對 LM 感染的抵抗力增加。使用Lipsoma巨噬細(xì)胞細(xì)胞清除劑Clodronateliposomes（CLL）。劑量是100ul，李斯特菌感染后2h注射。注射的劑量和時間點僅僅參考文獻(xiàn)。具體需要以自己的實驗?zāi)康臑闇?zhǔn)。比如為什么是100ul？為什么是感染后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.