PMID- 35391731
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220409
IS  - 1664-302X (Print)
IS  - 1664-302X (Electronic)
IS  - 1664-302X (Linking)
VI  - 13
DP  - 2022
TI  - Outer Membrane Vesicles From Fusobacterium nucleatum Switch M0-Like Macrophages 
      Toward the M1 Phenotype to Destroy Periodontal Tissues in Mice.
PG  - 815638
LID - 10.3389/fmicb.2022.815638 [doi]
LID - 815638
AB  - Periodontitis is a chronic inflammatory oral disease that affects nearly 50% of 
      all adults. Fusobacterium nucleatum (F. nucleatum) is known to be involved in the 
      formation and development of periodontitis. Outer membrane vesicles (OMVs) 
      harboring toxic bacterial components are continuously released during F. 
      nucleatum growth and regulate the extent of the inflammatory response by 
      controlling the functions of immune and non-immune cells in tissues. Macrophages 
      are important immune cells in periodontal tissue that resist pathogen invasion 
      and play an important role in the pathophysiological process of periodontitis. 
      However, the role of the interaction between F. nucleatum OMVs and macrophages in 
      the occurrence and development of periodontitis has not been studied. The purpose 
      of this study was to clarify the effect of F. nucleatum OMVs on the polarization 
      of macrophages and the roles of this specific polarization and F. nucleatum OMVs 
      in the pathophysiology of periodontitis. The periodontitis model was established 
      by inducing ligation in C57BL/6 mice as previously described. Micro-CT, RT-qPCR, 
      hematoxylin-eosin (H&E) and tartrate acid phosphatase (TRAP) staining assays were 
      performed to analyze the periodontal tissue, alveolar bone loss, number of 
      osteoclasts and expression of inflammatory factors in gingival tissue. The 
      changes in the state and cytokine secretion of bone marrow-derived macrophages 
      (BMDMs) stimulated by F. nucleatum OMVs were observed in vivo by confocal 
      microscopy, flow cytometry, Western blot and ELISA. Mouse gingival fibroblasts 
      (MGFs) were isolated and then cocultured with macrophages. The effects of F. 
      nucleatum OMVs on the proliferation and apoptosis of MGFs were analyzed by flow 
      cytometry and lactate dehydrogenase (LDH) assays. The periodontitis symptoms of 
      mice in the F. nucleatum OMVs + ligation group were more serious than those of 
      mice in the simple ligation group, with more osteoclasts and more inflammatory 
      factors (IL-1beta, IL-6, and TNF-alpha) being observed in their gingival tissues. M0 
      macrophages transformed into M1 macrophages after the stimulation of BMDMs with 
      F. nucleatum OMVs, and the M1 macrophages then released more inflammatory 
      cytokines. Analysis of the coculture model showed that the MGF apoptosis and LDH 
      release in the inflammatory environment were increased by F. nucleatum OMV 
      treatment. In conclusion, F. nucleatum OMVs were shown to aggravate 
      periodontitis, alveolar bone loss and the number of osteoclasts in an animal 
      model of periodontitis. F. nucleatum OMVs promoted the polarization of 
      macrophages toward the proinflammatory M1 phenotype, and the inflammatory 
      environment further aggravated the toxicity of F. nucleatum OMVs on MGFs. These 
      results suggest that M1 macrophages and F. nucleatum OMVs play roles in the 
      occurrence and development of periodontitis.
CI  - Copyright (c) 2022 Chen, Sun, Cai and Zhou.
FAU - Chen, Gang
AU  - Chen G
AD  - Shenzhen Stomatology Hospital (Pingshan), Southern Medical University, Shenzhen, 
      China.
FAU - Sun, Qiang
AU  - Sun Q
AD  - Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of 
      Zhengzhou University, Zhengzhou, China.
FAU - Cai, QiaoLing
AU  - Cai Q
AD  - Department of Stomatology, The First Affiliated Hospital of Xiamen University, 
      Xiamen, China.
FAU - Zhou, HongWei
AU  - Zhou H
AD  - Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, 
      Southern Medical University, Guangzhou, China.
AD  - State Key Laboratory of Organ Failure Research, Southern Medical University, 
      Guangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20220321
PL  - Switzerland
TA  - Front Microbiol
JT  - Frontiers in microbiology
JID - 101548977
PMC - PMC8981991
OTO - NOTNLM
OT  - Fusobacterium nucleatum
OT  - inflammation
OT  - macrophages
OT  - outer membrane vesicles
OT  - periodontitis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/09 06:00
MHDA- 2022/04/09 06:01
PMCR- 2022/03/21
CRDT- 2022/04/08 05:09
PHST- 2021/11/15 00:00 [received]
PHST- 2022/01/31 00:00 [accepted]
PHST- 2022/04/08 05:09 [entrez]
PHST- 2022/04/09 06:00 [pubmed]
PHST- 2022/04/09 06:01 [medline]
PHST- 2022/03/21 00:00 [pmc-release]
AID - 10.3389/fmicb.2022.815638 [doi]
PST - epublish
SO  - Front Microbiol. 2022 Mar 21;13:815638. doi: 10.3389/fmicb.2022.815638. 
      eCollection 2022.