2025年7月22日，哈佛医学院Dennis L. Kasper研究小组在《细胞》杂志发表论文，宣布他们的最新研究探明了肠道微生物糖脂结构调节宿主炎症反应。
课题组报道，共生脂质A的结构变化导致不同的免疫反应与每个脂质A结构，引发的影响不同于传统的脂质A诱导。某些脂质A结构可以诱导Cdc42介导的toll样受体4 （TLR4）内吞和脂滴（LD）形成介导的干扰素(IFN)-β反应。这种脂质A导向的IFN-β反应对于结肠RORγt+调节性T细胞（Treg）诱导至关重要，同时抑制结肠TH17细胞和控制肠道炎症。有趣的是，拟杆菌门中数量上占优势的五酰化脂质A不能引起IFN-β反应。相反，较少的四酰化脂质A可诱导IFN-β，从而促进RORγt+ Treg稳态。共生体脂质A结构的细微差别有助于维持Tregs的有效调节，以维持健康的内源性平衡。
研究人员表示，共生体不断地塑造着宿主的免疫景观。在革兰氏阴性微生物中发现的脂多糖在它们的外膜上有一个末端脂质A。
附：英文原文
Title: Structure of gut microbial glycolipid modulates host inflammatory response
Author: Hyoung-Soo Cho, Ji-Sun Yoo, Xinyang Song, Byoungsook Goh, Alos Diallo, Jesang Lee, Sumin Son, Yoon Soo Hwang, Seung Bum Park, Sungwhan F. Oh, Dennis L. Kasper
Issue&Volume: 2025-07-22
Abstract: Commensals are constantly shaping the host’s immunological landscape. Lipopolysaccharides found in gram-negative microbes have a terminal lipid A in their outer membrane. Here, we report that structural variations in symbiotic lipid A lead to divergent immune responses with each lipid A structure, eliciting effects distinct from those induced by classical lipid A. Certain lipid A structures can induce a sustained interferon (IFN)-β response orchestrated by Cdc42-facilitated Toll-like receptor 4 (TLR4) endocytosis and lipid droplet (LD) formation. This lipid A-directed IFN-β response is paramount for colon RORγt+ regulatory T cell (Treg) induction while simultaneously suppressing colonic TH17 cells and controlling gut inflammation. Intriguingly, the quantitatively dominant penta-acylated lipid A species in Bacteroidetes fails to elicit an IFN-β response. Instead, a less abundant tetra-acylated lipid A species sustainably induces IFN-β, thereby contributing to RORγt+ Treg homeostasis. Nuances in symbiont lipid A structure contribute to maintaining potent regulation of Tregs to maintain a healthy endobiotic balance.
DOI: 10.1016/j.cell.2025.05.016
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00566-5