The oral organism Tannerella forsythia is auxotrophic for peptidoglycan amino sugar N-acetylmuramic acid (MurNAc). It survives in the oral cavity by scavenging MurNAc- and MurNAc-linked peptidoglycan fragments (muropeptides) secreted by co-habiting bacteria such as Fusobacterium nucleatum with which it forms synergistic biofilms. Muropeptides, MurNAc-l-Ala-d-isoGln (MDP, muramyl dipeptide) and d-γ-glutamyl-meso-DAP (iE-DAP dipeptide), are strong immunostimulatory molecules that activate nucleotide oligomerization domain (NOD)-like innate immune receptors and induce the expression of inflammatory cytokines and antimicrobial peptides. In this study, we utilized an in vitro T. forsythia–F. nucleatum co-culture model to determine if T. forsythia can selectively scavenge NOD ligands from the environment and impact NOD-mediated inflammation. The results showed that NOD-stimulatory molecules were secreted by F. nucleatum in the spent culture broth, which subsequently induced cytokine and antimicrobial peptide expression in oral epithelial cells. In the spent broth from T. forsythia–F. nucleatum co-cultures, the NOD-stimulatory activity was significantly reduced. These data indicated that F. nucleatum releases NOD2-stimulatory muropeptides in the environment, and T. forsythia can effectively scavenge the muropeptides released by co-habiting bacteria to dampen NOD-mediated host responses. This proof-of-principle study demonstrated that peptidoglycan scavenging by T. forsythia can impact the innate immunity of oral epithelium by dampening NOD activation.

中文翻译：

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连翘坦纳菌清除具核梭杆菌分泌的NOD2刺激分子以抑制口腔上皮细胞炎症反应

口腔生物连翘坦纳菌(Tannerella forsythia)是肽聚糖氨基糖N-乙酰胞壁酸 (MurNAc) 营养缺陷型。它通过清除由具核梭杆菌等共生细菌分泌的 MurNAc 和 MurNAc 连接的肽聚糖片段（胞肽）在口腔中存活，并与这些细菌形成协同生物膜。Muropeptides、MurNAc- l -Ala- d -isoGln（MDP，胞壁酰二肽）和d -γ-谷氨酰-meso-DAP（iE-DAP 二肽）是强免疫刺激分子，可激活核苷酸寡聚结构域 (NOD) 样先天免疫受体并诱导炎症细胞因子和抗菌肽的表达。在这项研究中，我们利用体外连翘-具核镰刀菌共培养模型来确定连翘是否可以选择性地清除环境中的 NOD 配体并影响 NOD 介导的炎症。结果表明，废培养液中的具核梭杆菌分泌NOD刺激分子，随后诱导口腔上皮细胞中细胞因子和抗菌肽的表达。在连翘–F的废肉汤中。nucleatum共培养后，NOD 刺激活性显着降低。这些数据表明，F. nucleatum在环境中释放NOD2刺激性胞肽，而连翘可以有效清除共生细菌释放的胞肽，从而抑制NOD介导的宿主反应。这项原理验证研究表明，连翘清除肽聚糖可以通过抑制 NOD 激活来影响口腔上皮的先天免疫。