Microbial carriage state of peripheral blood dendritic cells (DCs) in chronic periodontitis influences DC differentiation, atherogenic potential

Julio Carrion, Elizabeth Scisci, Brodie Miles, Gregory J. Sabino, Amir E. Zeituni, Ying Gu, Adam Bear, Caroline A. Genco, David L. Brown, Christopher W. Cutler

Research output: Contribution to journalArticle

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Abstract

The low-grade oral infection chronic periodontitis (CP) has been implicated in coronary artery disease risk, but the mechanisms are unclear. In this study, a pathophysiological role for blood dendritic cells (DCs) in systemic dissemination of oral mucosal pathogens to atherosclerotic plaques was investigated in humans. The frequency and microbiome of CD19-BDCA- 1+DC-SIGN+ blood myeloid DCs (mDCs) were analyzed in CP subjects with or without existing acute coronary syndrome and in healthy controls. FACS analysis revealed a significant increase in blood mDCs in the following order: healthy controls < CP < acute coronary syndrome/CP. Analysis of the blood mDC microbiome by 16S rDNA sequencing showed Porphyromonas gingivalis and other species, including (cultivable) Burkholderia cepacia. The mDC carriage rate with P. gingivalis correlated with oral carriage rate and with serologic exposure to P. gingivalis in CP subjects. Intervention (local debridement) to elicit a bacteremia increased the mDC carriage rate and frequency in vivo. In vitro studies established that P. gingivalis enhanced by 28% the differentiation of monocytes into immature mDCs; moreover, mDCs secreted high levels of matrix metalloproteinase-9 and upregulated C1q, heat shock protein 60, heat shock protein 70, CCR2, and CXCL16 transcripts in response to P. gingivalis in a fimbriae-dependent manner. Moreover, the survival of the anaerobe P. gingivalis under aerobic conditions was enhanced when within mDCs. Immunofluorescence analysis of oral mucosa and atherosclerotic plaques demonstrate infiltration with mDCs, colocalized with P. gingivalis. Our results suggest a role for blood mDCs in harboring and disseminating pathogens from oral mucosa to atherosclerosis plaques, which may provide key signals for mDC differentiation and atherogenic conversion.

Original languageEnglish (US)
Pages (from-to)3178-3187
Number of pages10
JournalJournal of Immunology
Volume189
Issue number6
DOIs
StatePublished - Sep 15 2012

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Chronic Periodontitis
Porphyromonas gingivalis
Dendritic Cells
Cell Differentiation
Blood Cells
Microbiota
Mouth Mucosa
Atherosclerotic Plaques
Acute Coronary Syndrome
Chaperonin 60
Burkholderia cepacia
HSP70 Heat-Shock Proteins
Matrix Metalloproteinase 9
Debridement
Myeloid Cells
Bacteremia
Ribosomal DNA
Fluorescent Antibody Technique
Coronary Artery Disease
Monocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Microbial carriage state of peripheral blood dendritic cells (DCs) in chronic periodontitis influences DC differentiation, atherogenic potential. / Carrion, Julio; Scisci, Elizabeth; Miles, Brodie; Sabino, Gregory J.; Zeituni, Amir E.; Gu, Ying; Bear, Adam; Genco, Caroline A.; Brown, David L.; Cutler, Christopher W.

In: Journal of Immunology, Vol. 189, No. 6, 15.09.2012, p. 3178-3187.

Research output: Contribution to journalArticle

Carrion, Julio ; Scisci, Elizabeth ; Miles, Brodie ; Sabino, Gregory J. ; Zeituni, Amir E. ; Gu, Ying ; Bear, Adam ; Genco, Caroline A. ; Brown, David L. ; Cutler, Christopher W. / Microbial carriage state of peripheral blood dendritic cells (DCs) in chronic periodontitis influences DC differentiation, atherogenic potential. In: Journal of Immunology. 2012 ; Vol. 189, No. 6. pp. 3178-3187.
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AU - Bear, Adam

AU - Genco, Caroline A.

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