Enterococcus faecalis Induces Differentiation of Immune-Aberrant Dendritic Cells from Murine Bone Marrow-Derived Stem Cells

Abstract

Enterococcus faecalis (E. faecalis), long implicated in serious systemic infections and failure of root canal treatment, is a persistent inhabitant of oral periapical lesions. Dendritic cells (DCs) and other innate immune cells patrol the oral mucosa for infecting microbes. Dendritic cells are efficient at capturing microbes when immature, whereupon they can transform into potent antigen-presenting cells upon full maturation. Autophagy, a sophisticated intracellular process first described for elimination of damaged organelles, regulates DC maturation and other important immune functions of DCs. The present study examined how E. faecalis influences differentiation of murine bone marrow-derived stem cells (BMSCs) into functional DCs in the presence of the cytokines GM-CSF/IL4. Although the viability and differentiation of DCs were not affected by E. faecalis, expression of the autophagy-related proteins ATG7, Beclin1, and LC3bI/II were significantly suppressed in an mTOR-dependent manner. Ultrastructurally, E. faecalis were identified in single-membrane vacuoles, some of were in the process of binary fission. Bacteria-containing autophagosomes were absent within the cytoplasm. Accessory molecules (MHCII, CD80, CD86) and anti-inflammatory cytokine (TGFβ1) were suppressed in E. faecalis-induced DCs, while IL1β, TNFα and IL12 levels were upregulated. When pulsed with OVA, the E. faecalis-induced DCs showed reduction in CD4+ OVA-specific OTII T cells proliferation. It is concluded that E. faecalis promotes differentiation of bone marrow stem cells into CD11c-positive DCs with aberrant-immune functions while retaining the capability of pro-inflammatory cytokine induction.

Combined Transcriptomic and Protein Array Cytokine Profiling of Human Stem Cells from Dental Apical Papilla Modulated by Oral Bacteria

“…The ability of E. faecalis to downregulate the immune and inflammatory responses indicated a high virulence of the strain [46]. Consistent with previous studies, E. faecalis influenced bone marrow stem cell differentiation by promoting CD11c-positive dendritic cells with aberrant immune functions retaining the capability of proinflammatory cytokine induction [47]. Another study showed that E. faecalis in high doses slowed healing and suppressed the expression of inflammatory cytokines in a mouse model [48].…”

Enterococcus faecalis shifts macrophage polarization toward M1-like phenotype with an altered cytokine profile

“…Infection was maintained throughout the study by adding an additional dose of E. faecalis at day 6 with the same MOI. The rationale of using an MOI of 1 was to mimic chronic infection for a prolonged time with a low quantity of bacteria; a similar MOI was used for examining E. faecalis infection of BMSC-derived dendritic cells [18]. Infection of the already differentiated macrophages (post-M0 + E. faecalis) was performed at day 6 with an MOI of 1, to correlate and compare the effect of E. faecalis on macrophages before and after their differentiation.…”

The Effect of Photodynamic Therapy on Enterococcus spp. and Its Application in Dentistry: A Scoping Review

“…Interestingly, due to its resistance to antiseptics and disinfectants used in dental hygiene, E. faecalis is described as an essential cause of endodontic treatment failure, isolated in up to 77% of chronic and persistent periapical lesions cases [ 11 ]. In persistent intra-radicular E. faecalis infections, interaction with the host immune cells can lead to apical periodontitis that does not heal and can generate tissue destruction with bone resorption [ 12 , 13 ]. In this way, E. faecalis is considered the most significant species found in cases of duct systems with periradicular lesions [ 14 , 15 ].…”