Role of Enterococcus faecalis in refractory apical periodontitis: from pathogenicity to host cell response

ABSTRACT

Background: Refractory apical periodontitis (RAP) is an oral infectious disease characterised by persistent inflammation, progressive alveolar bone destruction, and delayed bone healing. RAP has received increasing attention, because it cannot be cured after repeated root canal therapies. The aetiology of RAP is related to the complex interplay between the pathogen and its host. However, the exact pathogenesis of RAP remains unclarified and includes several factors, such as microorganism immunogenicity, host immunity and inflammation, and tissue destruction and repair. Enterococcus faecalis is the dominant pathogen involved in RAP, and has evolved multiple strategies to ensure survival, which cause persistent intraradicular and extraradicular infections.

Objective: To review the crucial role of E. faecalis in the pathogenesis of RAP, and open new avenues for prevention and treatment of RAP.

Methods: The PubMed and Web of Science databases were searched for pertinent publications, employing the search terms “Enterococcus faecalis”, “refractory apical periodontitis”, “persistent periapical periodontitis”, “pathogenicity”, “virulence”, “biofilm formation”, “dentine tubule”, “immune cell”, “macrophage”, and “osteoblast”.

Results and Conclusion: Besides its high pathogenicity due to various virulence mechanisms, E. faecalis modulates the macrophage and osteoblast responses, including regulated cell death, cell polarisation, cell differentiation, and inflammatory response. An in-depth understanding of the multifaceted host cell responses modulated by E. faecalis will help to design potential future therapeutic strategies and overcome the challenges of sustained infection and delayed tissue healing in RAP.

KEYWORDS:

• Enterococcus faecalis
• macrophage
• osteoblast
• refractory apical periodontitis
• virulence
• regulated cell death
• differentiation
• polarisation

Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China under Grant [number 82100997]; the Natural Science Foundation of Guangdong Province under Grant [number 2022A1515012169]; the Science and Technology Program of Guangzhou under Grant [number 202201010983]; the President Foundation of Nanfang Hospital, Southern Medical University under Grant [number 2019Z019]; the Clinical Research Program of Southern Medical University under Grant [number LC2019ZD023]; the Clinical Research Program of Nanfang Hospital, Southern Medical University under Grant [number 2020CR029 and 2021CR011] and the Scientific Research Initiation Program of Southern Medical University under Grant [number B521NF0033].

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by grants from the National Natural Science Foundation of China [number 82100997]; the Science and Technology Program of Guangzhou [number 202201010983]; the Natural Science Foundation of Guangdong Province [number 2022A1515012169]; the President Foundation of Nanfang Hospital, Southern Medical University [number 2019Z019]; the Clinical Research Program of Southern Medical University [number LC2019ZD023]; the Clinical Research Program of Nanfang Hospital, Southern Medical University [number 2020CR029 and 2021CR011], the Scientific Research Initiation Program of Southern Medical University [number B521NF0033] and the College Students' Innovative Entrepreneurial Training Plan Program [number 202212121240].