DnaK of Parvimonas micra OMVs interacted with the host fibroblast Bag3-IKK-γ axis to accelerate TNF-α secretion in oral lichen planus

Author:

Ji Xiaoli1,Zhi Mengfan2,Gu Xiufeng2,Han Ying3,Lan Xiang2,Song lixiang2,Sun Peipei1,Li Jingyuan2,Qi XiangMin2,Feng Qiang2

Affiliation:

1. Central Hospital Affiliated to Shandong First Medical University

2. Shandong University

3. Peking University School and Hospital of Stomatology

Abstract

Abstract

Background Oral lichen planus (OLP) is one of the most frequent oral mucosal diseases associated with chronic inflammation despite extremely insufficient knowledge of its pathogenic mechanism.Results Here, the microbiome of buccal and lip mucosae, tongue dorsum and saliva among OLP patients and healthy individuals was analyzed. It was found that the oral microbiome, especially the buccal mucosa, varied significantly in OLP patients. Network, random forest and Netshift analyses simultaneously showed that Parvimonas micra (P. micra) was an important bacterium of OLP disease. Fluorescence in situ hybridization (FISH) and single-cell ribonucleic acid (RNA) sequencing profiling suggested that fibroblasts were the candidate target with the characteristic of up-regulating the nuclear factor kappa-B (NF-қB) signaling pathway related to tumor necrosis factor-alpha (TNF-α) and communicating with multiple immune cell types. Mechanism analysis showed that P. micra, P. micra-derived conditional medium (CM) and outer membrane vesicles (OMVs) could induce the activity of NF-қB signaling pathway and inhibit autophagy in buccal mucosal fibroblasts. As one of the main pathogenic effectors, the DnaK of P. micra-derived OMVs could inhibit autophagy and promote TNF-α secretion via the DnaK-Bcl-2 associated athanogene 3 (Bag3)-inhibitor of nuclear factor kappa-B kinase subunit gamma (IKK-γ) signaling axis.Conclusions Here we demonstrate that P. micra’s OMV drives OLP via DnaK -Bag3-IKK-γ/NF-қB signaling axis in the fibroblasts as new insights into the pathogenic mechanism of OLP.

Publisher

Springer Science and Business Media LLC

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