Systemic antibiotic therapy reduces circulating inflammatory dendritic cells and Treg–Th17 plasticity in periodontitis

Mythilypriya Rajendran, Stephen Warwick Looney, Nagendra Singh, Mahmoud Elashiry, Mohamed M. Meghil, Ahmed R. El-Awady, Omnia Tawfik, Cristiano Susin, Roger Mauricio Arce Munoz, Christopher W Cutler

Research output: Contribution to journalArticle

Abstract

Periodontitis (PD) is a common dysbiotic inflammatory disease that leads to local bone deterioration and tooth loss. PD patients experience low-grade bacteremias with oral microbes implicated in the risk of heart disease, cancer, and kidney failure. Although Th17 effectors are vital to fighting infection, functional imbalance of Th17 effectors and regulatory T cells (Tregs) promote inflammatory diseases. In this study, we investigated, in a small pilot randomized clinical trial, whether expansion of inflammatory blood myeloid dendritic cells (DCs) and conversion of Tregs to Th17 cells could be modulated with antibiotics (AB) as part of initial therapy in PD patients. PD patients were randomly assigned to either 7 d of peroral metronidazole/amoxicillin AB treatment or no AB, along with standard care debridement and chlorhexidine mouthwash. 16s ribosomal RNA analysis of keystone pathogen Porphyromonas gingivalis and its consortium members Fusobacterium nucleatum and Streptococcus gordonii confirmed the presence of all three species in the reservoirs (subgingival pockets and blood DCs) of PD patients before treatment. Of the three species, P. gingivalis was reduced in both reservoirs 4–6 wk after therapy. Further, the frequency of CD1C+CCR6+ myeloid DCs and IL-1R1 expression on IL-17A+FOXP3+CD4+ T cells in PD patients were reduced to healthy control levels. The latter led to decreased IL-1b–stimulated Treg plasticity in PD patients and improvement in clinical measures of PD. Overall, we identified an important, albeit short-term, beneficial role of AB therapy in reducing inflammatory DCs and Treg–Th17 plasticity in humans with PD.

Original languageEnglish (US)
Pages (from-to)2690-2699
Number of pages10
JournalJournal of Immunology
Volume202
Issue number9
DOIs
StatePublished - May 1 2019

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Periodontitis
Dendritic Cells
Anti-Bacterial Agents
Porphyromonas gingivalis
Therapeutics
Myeloid Cells
Blood Cells
Streptococcus gordonii
Fusobacterium nucleatum
Mouthwashes
16S Ribosomal RNA
Cell Plasticity
Th17 Cells
Tooth Loss
Heart Neoplasms
Chlorhexidine
Interleukin-17
Kidney Neoplasms
Amoxicillin
Metronidazole

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Systemic antibiotic therapy reduces circulating inflammatory dendritic cells and Treg–Th17 plasticity in periodontitis. / Rajendran, Mythilypriya; Looney, Stephen Warwick; Singh, Nagendra; Elashiry, Mahmoud; Meghil, Mohamed M.; El-Awady, Ahmed R.; Tawfik, Omnia; Susin, Cristiano; Arce Munoz, Roger Mauricio; Cutler, Christopher W.

In: Journal of Immunology, Vol. 202, No. 9, 01.05.2019, p. 2690-2699.

Research output: Contribution to journalArticle

Rajendran, Mythilypriya ; Looney, Stephen Warwick ; Singh, Nagendra ; Elashiry, Mahmoud ; Meghil, Mohamed M. ; El-Awady, Ahmed R. ; Tawfik, Omnia ; Susin, Cristiano ; Arce Munoz, Roger Mauricio ; Cutler, Christopher W. / Systemic antibiotic therapy reduces circulating inflammatory dendritic cells and Treg–Th17 plasticity in periodontitis. In: Journal of Immunology. 2019 ; Vol. 202, No. 9. pp. 2690-2699.
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AU - Rajendran, Mythilypriya

AU - Looney, Stephen Warwick

AU - Singh, Nagendra

AU - Elashiry, Mahmoud

AU - Meghil, Mohamed M.

AU - El-Awady, Ahmed R.

AU - Tawfik, Omnia

AU - Susin, Cristiano

AU - Arce Munoz, Roger Mauricio

AU - Cutler, Christopher W

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AB - Periodontitis (PD) is a common dysbiotic inflammatory disease that leads to local bone deterioration and tooth loss. PD patients experience low-grade bacteremias with oral microbes implicated in the risk of heart disease, cancer, and kidney failure. Although Th17 effectors are vital to fighting infection, functional imbalance of Th17 effectors and regulatory T cells (Tregs) promote inflammatory diseases. In this study, we investigated, in a small pilot randomized clinical trial, whether expansion of inflammatory blood myeloid dendritic cells (DCs) and conversion of Tregs to Th17 cells could be modulated with antibiotics (AB) as part of initial therapy in PD patients. PD patients were randomly assigned to either 7 d of peroral metronidazole/amoxicillin AB treatment or no AB, along with standard care debridement and chlorhexidine mouthwash. 16s ribosomal RNA analysis of keystone pathogen Porphyromonas gingivalis and its consortium members Fusobacterium nucleatum and Streptococcus gordonii confirmed the presence of all three species in the reservoirs (subgingival pockets and blood DCs) of PD patients before treatment. Of the three species, P. gingivalis was reduced in both reservoirs 4–6 wk after therapy. Further, the frequency of CD1C+CCR6+ myeloid DCs and IL-1R1 expression on IL-17A+FOXP3+CD4+ T cells in PD patients were reduced to healthy control levels. The latter led to decreased IL-1b–stimulated Treg plasticity in PD patients and improvement in clinical measures of PD. Overall, we identified an important, albeit short-term, beneficial role of AB therapy in reducing inflammatory DCs and Treg–Th17 plasticity in humans with PD.

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