PMID- 32839187 OWN - NLM STAT- MEDLINE DCOM- 20210325 LR - 20220421 IS - 1098-5522 (Electronic) IS - 0019-9567 (Print) IS - 0019-9567 (Linking) VI - 88 IP - 11 DP - 2020 Oct 19 TI - Enterococcus faecalis Induces Differentiation of Immune-Aberrant Dendritic Cells from Murine Bone Marrow-Derived Stem Cells. LID - 10.1128/IAI.00338-20 [doi] LID - e00338-20 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 (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 beta1 [TGF-beta1]) were suppressed in E. faecalis-induced DCs, while IL-1beta, tumor necrosis factor alpha (TNF-alpha), 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. CI - Copyright (c) 2020 American Society for Microbiology. FAU - Elashiry, Mohamed Mohamed AU - Elashiry MM AUID- ORCID: 0000-0003-0880-4882 AD - Department of Periodontics, The Dental College of Georgia, Augusta University, Augusta, Georgia, USA. AD - Department of Endodontics, Faculty of Dentistry, Ain Shams University, Cairo, Egypt. FAU - Elashiry, Mahmoud AU - Elashiry M AUID- ORCID: 0000-0001-7077-2725 AD - Department of Periodontics, The Dental College of Georgia, Augusta University, Augusta, Georgia, USA. FAU - Zeitoun, Rana AU - Zeitoun R AD - Department of Oral Biology and Diagnostic Science, The Dental College of Georgia, Augusta University, Augusta, Georgia, USA. AD - Department of Fixed Prosthodontics, Faculty of Dentistry, Ain Shams University, Cairo, Egypt. FAU - Elsayed, Ranya AU - Elsayed R AD - Department of Periodontics, The Dental College of Georgia, Augusta University, Augusta, Georgia, USA. FAU - Tian, Fucong AU - Tian F AD - Department of Endodontics, The Dental College of Georgia, Augusta University, Augusta, Georgia, USA. FAU - Saber, Shehab Eldin AU - Saber SE AD - Department of Endodontics, Faculty of Dentistry, Ain Shams University, Cairo, Egypt. AD - Department of Endodontics, Faculty of Dentistry, The British University in Egypt, Cairo, Egypt. FAU - Elashry, Salma Hasan AU - Elashry SH AD - Department of Endodontics, Faculty of Dentistry, Ain Shams University, Cairo, Egypt. FAU - Tay, Franklin R AU - Tay FR AD - Department of Endodontics, The Dental College of Georgia, Augusta University, Augusta, Georgia, USA. FAU - Cutler, Christopher W AU - Cutler CW AUID- ORCID: 0000-0003-4396-4072 AD - Department of Periodontics, The Dental College of Georgia, Augusta University, Augusta, Georgia, USA chcutler@augusta.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201019 PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 SB - IM MH - Animals MH - Cell Differentiation/*immunology MH - Dendritic Cells/*immunology MH - Enterococcus faecalis/*immunology MH - Gram-Positive Bacterial Infections/*immunology MH - Hematopoietic Stem Cells/*immunology MH - Mice PMC - PMC7573447 OTO - NOTNLM OT - Enterococcus faecalis OT - antigen presentation OT - autophagy OT - bone marrow-derived stem cells OT - dendritic cells OT - infection OT - inflammatory cytokines EDAT- 2020/08/26 06:00 MHDA- 2021/03/26 06:00 PMCR- 2021/04/19 CRDT- 2020/08/26 06:00 PHST- 2020/06/08 00:00 [received] PHST- 2020/08/19 00:00 [accepted] PHST- 2020/08/26 06:00 [pubmed] PHST- 2021/03/26 06:00 [medline] PHST- 2020/08/26 06:00 [entrez] PHST- 2021/04/19 00:00 [pmc-release] AID - IAI.00338-20 [pii] AID - 00338-20 [pii] AID - 10.1128/IAI.00338-20 [doi] PST - epublish SO - Infect Immun. 2020 Oct 19;88(11):e00338-20. doi: 10.1128/IAI.00338-20. Print 2020 Oct 19.