中文摘要：

致病性病毒感染是人类健康面临的重大挑战。宿主对呼吸道病毒的免疫反应通过肠肺轴与微生物组和新陈代谢密切相关。宿主对甲型流感病毒 （IAV） 的防御涉及激活 NLRP3 炎性小体，然而，NLRP3 保护功能背后的机制尚不清楚。在这里，我们表明一种分离的细菌菌株，假长双歧杆菌 NjM1，富含 Nlrp3 - / - 小鼠的肠道微生物群，保护野生型而不是 Nlrp3 缺陷小鼠免受 IAV 感染。这种作用取决于 NjM1 衍生的乙酸盐介导的 I 型干扰素 （IFN-I） 的增强产生。外源性乙酸盐的应用再现了 NjM1 的保护作用。从机制上讲，NLRP3 桥接 GPR43 和 MAVS，并促进 MAVS 的寡聚化和信号传导;而乙酸盐在 GPR43 参与后增强 MAVS 聚集，导致 IFN-I 产生增加。因此，我们的数据支持 NLRP3 通过产生乙酸盐的细菌介导增强 IFN-I 诱导的模型，并表明乙酸盐-GPR43-NLRP3-MAVS-IFN-I 信号轴是针对呼吸道病毒感染的潜在治疗靶点。

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.

论文信息：

论文题目：Microbiota-derived acetate enhances host antiviral response via NLRP3

期刊名称：Nature Communications

时间期卷：14, Article number: 642 (2023)

在线时间：2024年2月6日

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

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）

氯膦酸盐二钠脂质体清除单核巨噬细胞，在呼吸道病毒感染模型中单核巨噬细胞功能研究，荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications：Clodronate Liposomes清除肺脏巨噬细胞助力呼吸道病毒感染模型研究

Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法：

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.