TY - JOUR
T1 - Systemic antibiotic therapy reduces circulating inflammatory dendritic cells and Treg–Th17 plasticity in periodontitis
AU - Rajendran, Mythilypriya
AU - Looney, Stephen
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.
N1 - Funding Information:
This work was supported in part by grants from the National Institutes of Health-National Institute of Dental and Craniofacial Research (R01 DE014328) and the Carlos and Marguerite Mason Trust to improve kidney transplant outcomes in Georgia (to C.W.C.).
Funding Information:
This work was supported in part by grants from the National Institutes of Health-National Institute of Dental and Craniofacial Research (R01 DE014328) and the Carlos and Marguerite Mason Trust to improve kidney transplant outcomes in Georgia (to C.W.C.). We are grateful to David Munn (Augusta University, Augusta, GA) for the expertise and feedback. We thank Zoya B. Kurago (Augusta University, Augusta, GA) for helpful scientific discussion. We gratefully acknowledge Jing Sun for her assistance with the statistical analyses and graphics.
Publisher Copyright:
Copyright © 2019 by The American Association of Immunologists, Inc.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
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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U2 - 10.4049/jimmunol.1900046
DO - 10.4049/jimmunol.1900046
M3 - Article
C2 - 30944162
AN - SCOPUS:85065112036
SN - 0022-1767
VL - 202
SP - 2690
EP - 2699
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -