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

Mohamed Mohamed Elashiry; Mahmoud Elashiry; Rana Zeitoun; Ranya Elsayed; Fucong Tian; Shehab Eldin Saber; Salma Hasan Elashry; Franklin R Tay; Christopher W Cutler

doi:10.1128/IAI.00338-20

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

Infect Immun. 2020 Oct 19;88(11):e00338-20. doi: 10.1128/IAI.00338-20. Print 2020 Oct 19.

Authors

Mohamed Mohamed Elashiry^{1

2}, Mahmoud Elashiry¹, Rana Zeitoun^{3

4}, Ranya Elsayed¹, Fucong Tian⁵, Shehab Eldin Saber^{2

6}, Salma Hasan Elashry², Franklin R Tay⁵, Christopher W Cutler⁷

Affiliations

¹ Department of Periodontics, The Dental College of Georgia, Augusta University, Augusta, Georgia, USA.
² Department of Endodontics, Faculty of Dentistry, Ain Shams University, Cairo, Egypt.
³ Department of Oral Biology and Diagnostic Science, The Dental College of Georgia, Augusta University, Augusta, Georgia, USA.
⁴ Department of Fixed Prosthodontics, Faculty of Dentistry, Ain Shams University, Cairo, Egypt.
⁵ Department of Endodontics, The Dental College of Georgia, Augusta University, Augusta, Georgia, USA.
⁶ Department of Endodontics, Faculty of Dentistry, The British University in Egypt, Cairo, Egypt.
⁷ Department of Periodontics, The Dental College of Georgia, Augusta University, Augusta, Georgia, USA chcutler@augusta.edu.

Abstract

Enterococcus 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 the differentiation of murine bone marrow-derived stem cells (BMSCs) into functional DCs in the presence of the cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). 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 was identified in single-membrane vacuoles, some of which were in the process of binary fission. Bacterium-containing autophagosomes were absent within the cytoplasm. Accessory molecules (major histocompatibility complex class II [MHC-II], CD80, and CD86) and anti-inflammatory cytokine (transforming growth factor β1 [TGF-β1]) were suppressed in E. faecalis-induced DCs, while IL-1β, tumor necrosis factor alpha (TNF-α), and IL-12 levels were upregulated. When pulsed with ovalbumin (OVA), the E. faecalis-induced DCs showed reduction in CD4⁺ OVA-specific OT-II T cell proliferation. It is concluded that E. faecalis promotes the differentiation of bone marrow stem cells into CD11c-positive DCs with aberrant immune functions while retaining the capability of proinflammatory cytokine induction.

Keywords: Enterococcus faecalis; antigen presentation; autophagy; bone marrow-derived stem cells; dendritic cells; infection; inflammatory cytokines.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation / immunology*
Dendritic Cells / immunology*
Enterococcus faecalis / immunology*
Gram-Positive Bacterial Infections / immunology*
Hematopoietic Stem Cells / immunology*
Mice