TY - JOUR
T1 - Enterococcus faecalis induces differentiation of immune-aberrant dendritic cells from murine bone marrow-derived stem cells
AU - Elashiry, Mohamed Mohamed
AU - Elashiry, Mahmoud
AU - Zeitoun, Rana
AU - Elsayed, Ranya
AU - Tian, Fucong
AU - Saber, Shehab Eldin
AU - Elashry, Salma Hasan
AU - Tay, Franklin R.
AU - Cutler, Christopher W.
N1 - Funding Information:
Funding for this work was provided by a grant from the Carlos and Marguerite Mason Trust Foundation and the Augusta University Office of Vice President of Research intramural grants program.
Funding Information:
Funding for this work was provided by a grant from the Carlos and Marguerite Mason Trust Foundation and the Augusta University Office of Vice President of Research intramural grants program. We declare no potential conflicts of interest with respect to the authorship and/or publication of this article. Mohamed Mohamed Elashiry contributed to conception, design, data acquisition and interpretation, and analysis and drafted and critically revised the manuscript. Mahmoud Elashiry contributed to design and data acquisition and interpretation and critically revised the manuscript. Rana Zeitoun, Ranya Elsayed, and Fucong Tian contributed to data acquisition and critically revised the manuscript. Shehab Eldin Saber and Salma Hasan Elashry contributed to data interpretation and critically revised the manuscript. Franklin R. Tay contributed to data interpretation and drafted and critically revised the manuscript. Christopher W. Cutler contributed to conception, design, and data interpretation and drafted and critically revised the manuscript. All authors gave their final approval and agreed to be accountable for all aspects of the work.
Publisher Copyright:
© 2020 American Society for Microbiology.
PY - 2020/11
Y1 - 2020/11
N2 - 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 (GMCSF) 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.
AB - 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 (GMCSF) 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.
KW - Antigen presentation
KW - Autophagy
KW - Bone marrow-derived stem cells
KW - Dendritic cells
KW - Enterococcus faecalis
KW - Infection
KW - Inflammatory cytokines
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U2 - 10.1128/IAI.00338-20
DO - 10.1128/IAI.00338-20
M3 - Article
C2 - 32839187
AN - SCOPUS:85093894077
SN - 0019-9567
VL - 88
JO - Infection and Immunity
JF - Infection and Immunity
IS - 11
M1 - e00338-20
ER -
