Systemic Antibiotic Therapy Reduces Circulating Inflammatory Dendritic Cells and Treg–Th17 Plasticity in Periodontitis

• Published in: The Journal of immunology (1950) Vol. 202; no. 9; pp. 2690 - 2699
• Main Authors: Rajendran, Mythilypriya, Looney, Stephen, Singh, Nagendra, Elashiry, Mahmoud, Meghil, Mohamed M, El-Awady, Ahmed R, Tawfik, Omnia, Susin, Cristiano, Arce, Roger M, Cutler, Christopher W
• Format: Journal Article
• Language: English
• Published: United States 01.05.2019
• Subjects: Amoxicillin - administration & dosage; Bacteria - immunology; Bacteria - metabolism; Bacterial Infections - blood; Bacterial Infections - drug therapy; Bacterial Infections - immunology; Bacterial Infections - pathology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - pathology; Female; Humans; Male; Metronidazole - administration & dosage; Middle Aged; Periodontitis - blood; Periodontitis - drug therapy; Periodontitis - immunology; Periodontitis - pathology; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - parasitology; T-Lymphocytes, Regulatory - pathology; Th17 Cells - immunology; Th17 Cells - metabolism; Th17 Cells - pathology
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.1900046

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-1β–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.