Clodronate Liposomes清除肺臟巨噬細(xì)胞助力呼吸道病毒感染模型研究

中文摘要：

致病性病毒感染是人類健康面臨的重大挑戰(zhàn)。宿主對呼吸道病毒的免疫反應(yīng)通過腸肺軸與微生物組和新陳代謝密切相關(guān)。宿主對甲型流感病毒 （IAV） 的防御涉及激活 NLRP3 炎性小體，然而，NLRP3 保護(hù)功能背后的機(jī)制尚不清楚。在這里，我們表明一種分離的細(xì)菌菌株，假長雙歧桿菌 NjM1，富含 Nlrp3 - / - 小鼠的腸道微生物群，保護(hù)野生型而不是 Nlrp3 缺陷小鼠免受 IAV 感染。這種作用取決于 NjM1 衍生的乙酸鹽介導(dǎo)的 I 型干擾素 （IFN-I） 的增強(qiáng)產(chǎn)生。外源性乙酸鹽的應(yīng)用再現(xiàn)了 NjM1 的保護(hù)作用。從機(jī)制上講，NLRP3 橋接 GPR43 和 MAVS，并促進(jìn) MAVS 的寡聚化和信號傳導(dǎo);而乙酸鹽在 GPR43 參與后增強(qiáng) MAVS 聚集，導(dǎo)致 IFN-I 產(chǎn)生增加。因此，我們的數(shù)據(jù)支持 NLRP3 通過產(chǎn)生乙酸鹽的細(xì)菌介導(dǎo)增強(qiáng) IFN-I 誘導(dǎo)的模型，并表明乙酸鹽-GPR43-NLRP3-MAVS-IFN-I 信號軸是針對呼吸道病毒感染的潛在治療靶點(diǎn)。

英文摘要：

Pathogenic viral infections represent a major challenge to human health. Host immune responses to respiratory viruses are closely associated with microbiome and metabolism via the gut-lung axis. It has been known that host defense against influenza A virus (IAV) involves activation of the NLRP3 inflammasome, however, mechanisms behind the protective function of NLRP3 are not fully known. Here we show that an isolated bacterial strain, Bifidobacterium pseudolongum NjM1, enriched in the gut microbiota of Nlrp3?/? mice, protects wild-type but not Nlrp3 deficient mice against IAV infection. This effect depends on the enhanced production of type I interferon (IFN-I) mediated by NjM1-derived acetate. Application of exogenous acetate reproduces the protective effect of NjM1. Mechanistically, NLRP3 bridges GPR43 and MAVS, and promotes the oligomerization and signalling of MAVS; while acetate enhances MAVS aggregation upon GPR43 engagement, leading to elevated IFN-I production. Thus, our data support a model of NLRP3 mediating enhanced induction of IFN-I via acetate-producing bacterium and suggest that the acetate-GPR43-NLRP3-MAVS-IFN-I signalling axis is a potential therapeutic target against respiratory viral infections.

論文信息：

論文題目：Microbiota-derived acetate enhances host antiviral response via NLRP3

期刊名稱：Nature Communications

時間期卷：14, Article number: 642 (2023)

在線時間：2024年2月6日

DOI：doi.org/10.1038/s41467-023-36323-4

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(diǎn)科技）

氯膦酸鹽二鈉脂質(zhì)體清除單核巨噬細(xì)胞，在呼吸道病毒感染模型中單核巨噬細(xì)胞功能研究，荷蘭Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見刊于Nature Communications：Clodronate Liposomes清除肺臟巨噬細(xì)胞助力呼吸道病毒感染模型研究

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：

Macrophage depletion

WT mice were pretreated with sodium acetate (SA) or drinking water and then intranasally administered with 100?μL of clodronate (LIPOSOMA, C28J0620) to deplete macrophages in the lung. The cell number of alveolar macrophages in BALF were analyzed by flow cytometry.