Enterococcus faecalis Extracellular Vesicles Promote Apical Periodontitis

Enterococcus faecalis Extracellular Vesicles Promote Apical Periodontitis

Enterococcus faecalis is an important contributor to the persistence of chronic apical periodontitis. However, the mechanism by which E. faecalis infection in the root canals and dentinal tubules affects periapical tissue remains unclear. Bacterial extracellular vesicles (EVs) act as natural carrier...

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Bibliographic Details
Published in:Journal of dental research Vol. 103; no. 6; pp. 672 - 682
Main Authors: Ma, R.Y., Deng, Z.L., Du, Q.Y., Dai, M.Q., Luo, Y.Y., Liang, Y.E., Dai, X.Z., Guo, S.M., Zhao, W.H.
Format: Journal Article
Language:English
Published: Los Angeles, CA SAGE Publications 01-06-2024
SAGE PUBLICATIONS, INC
Subjects:
Bacteria
Bacterial vesicles
Chronic infection
Enterococcus faecalis
Extracellular vesicles
Gum disease
Immunofluorescence
Inflammation
Internalization
Macrophages
NOD2 protein
Pathogenesis
Pattern recognition receptors
Periodontitis
Polarization
Root canals
Tubules
Ubiquitination
Virulence factors
pattern recognition receptors
macrophage
NOD2
RIPK2
ubiquitination
extracellular vesicle
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Summary:Enterococcus faecalis is an important contributor to the persistence of chronic apical periodontitis. However, the mechanism by which E. faecalis infection in the root canals and dentinal tubules affects periapical tissue remains unclear. Bacterial extracellular vesicles (EVs) act as natural carriers of microbe-associated molecular patterns (MAMPs) and have recently attracted considerable attention. In this study, we investigated the role of EVs derived from E. faecalis in the pathogenesis of apical periodontitis. We observed that E. faecalis EVs can induce inflammatory bone destruction in the periapical areas of mice. Double-labeling immunofluorescence indicated that M1 macrophage infiltration was increased by E. faecalis EVs in apical lesions. Moreover, in vitro experiments demonstrated the internalization of E. faecalis EVs into macrophages. Macrophages tended to polarize toward the M1 profile after treatment with E. faecalis EVs. Pattern recognition receptors (PRRs) can recognize MAMPs of bacterial EVs and, in turn, trigger inflammatory responses. Thus, we performed further mechanistic exploration, which showed that E. faecalis EVs considerably increased the expression of NOD2, a cytoplasmic PRR, and that inhibition of NOD2 markedly reduced macrophage M1 polarization induced by E. faecalis EVs. RIPK2 ubiquitination is a major downstream of NOD2. We also observed increased RIPK2 ubiquitination in macrophages treated with E. faecalis EVs, and E. faecalis EV-induced macrophage M1 polarization was notably alleviated by the RIPK2 ubiquitination inhibitor. Our study revealed the potential for EVs to be considered a virulence factor of E. faecalis and found that E. faecalis EVs can promote macrophage M1 polarization via NOD2/RIPK2 signaling. To our knowledge, this is the first report to investigate apical periodontitis development from the perspective of bacterial vesicles and demonstrate the role and mechanism of E. faecalis EVs in macrophage polarization. This study expands our understanding of the pathogenic mechanism of E. faecalis and provides novel insights into the pathogenesis of apical periodontitis.
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content type line 23
ISSN:0022-0345
1544-0591
1544-0591
DOI:10.1177/00220345241230867