Microbial nucleic acids represent a group of microbe-associated molecular patterns that are recognized through intracellular innate sensors triggering inflammatory responses. Toll like receptor 9 (TLR9) is the major receptor for microbial DNA. Using a reverse translational approach, we revealed that TLR9 contributes to periodontal disease pathogenesis through exacerbating the local inflammatory responses. Current proposal will extend our previous studies to fully characterize the biological pathways and cellular sources of TLR9-triggered inflammation in periodontitis. We will determine both the non-redundant as well as cooperative role of TLR9 with other innate sensors implicated in periodontitis. The effect of TLR9 inhibitors to periodontal disease outcome will also be evaluated. Periodontal disease is not only limited to gingival tissues but also is associated with various systemic diseases. Identification of periodontal microbial DNA at distant sites suggests that microbial nucleic acid sensing may not be only important in periodontal disease pathogenesis but also contributes to periodontal disease adverse effects on systemic health. Therefore, the proposed studies will not only identify novel biological pathways and therapeutic targets to control local persistent periodontal inflammation but also lead to future investigations to identify a novel link between periodontitis and systemic complications.

Public Health Relevance

Current proposal will characterize the involvement of microbial nucleic sensing in periodontal inflammation. The main focus will be TLR9-triggered inflammatory responses. The proposed studies will reveal novel biological pathways and therapeutic targets to control and prevent periodontitis and will lead to future studies to identif novel link between periodontitis and systemic complications.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE025037-02
Application #
9094493
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Chander, Preethi
Project Start
2015-06-20
Project End
2020-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Dentistry
Type
Schools of Dentistry/Oral Hygn
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Song, Kyung-A; Niederst, Matthew J; Lochmann, Timothy L et al. (2018) Epithelial-to-Mesenchymal Transition Antagonizes Response to Targeted Therapies in Lung Cancer by Suppressing BIM. Clin Cancer Res 24:197-208
Acharya, Chathur; Sahingur, Sinem Esra; Bajaj, Jasmohan S (2017) Microbiota, cirrhosis, and the emerging oral-gut-liver axis. JCI Insight 2:
Crump, Katie E; Oakley, Jennifer C; Xia-Juan, Xia et al. (2017) Interplay of Toll-Like Receptor 9, Myeloid Cells, and Deubiquitinase A20 in Periodontal Inflammation. Infect Immun 85:
Ramôa, C P; Eissenberg, T; Sahingur, S E (2017) Increasing popularity of waterpipe tobacco smoking and electronic cigarette use: Implications for oral healthcare. J Periodontal Res 52:813-823
Walsh, Scott W; Chumble, Anuja A; Washington, Sonya L et al. (2017) Increased expression of toll-like receptors 2 and 9 is associated with reduced DNA methylation in spontaneous preterm labor. J Reprod Immunol 121:35-41
Crump, K E; Sahingur, S E (2016) Microbial Nucleic Acid Sensing in Oral and Systemic Diseases. J Dent Res 95:17-25