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Microbial Nucleic Acid Sensing in Oral and Systemic Diseases
1Department of Periodontics, School of Dentistry, Virginia Commonwealth University, Richmond, VA, USA.
Abstract:
One challenge in studying chronic infectious and inflammatory disorders is understanding how host pattern recognition receptors (PRRs), specifically toll-like receptors (TLRs), sense and respond to pathogen- or damage-associated molecular patterns, their communication with each other and different components of the immune system, and their role in propagating inflammatory stages of disease. The discovery of innate immune activation through nucleic acid recognition by intracellular PRRs such as endosomal TLRs (TLR3, TLR7, TLR8, and TLR9) and cytoplasmic proteins (absent in melanoma 2 and DNA-dependent activator of interferon regulatory factor) opened a new paradigm: Nucleic acid sensing is now implicated in multiple immune and inflammatory conditions (e.g., atherosclerosis, cancer), viral (e.g., human papillomavirus, herpes virus) and bacterial (e.g., Helicobacter pylori, pneumonia) diseases, and autoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis). Clinical investigations reveal the overexpression of specific nucleic acid sensors in diseased tissues. In vivo animal models show enhanced disease progression associated with receptor activation. The involvement of nucleic acid sensors in various systemic conditions is further supported by studies reporting receptor knockout mice being either protected from or prone to disease. TLR9-mediated inflammation is also implicated in periodontal diseases. Considering that persistent inflammation in the oral cavity is associated with systemic diseases and that oral microbial DNA is isolated at distal sites, nucleic acid sensing may potentially be a link between oral and systemic diseases. In this review, we discuss recent advances in how intracellular PRRs respond to microbial nucleic acids and emerging views on the role of nucleic acid sensors in various systemic diseases. We also highlight new information on the role of intracellular PRRs in the pathogenesis of oral diseases including periodontitis and oral cavity cancer, which might offer future possibilities for disease prevention and therapy.
Insights
Host pattern recognition receptors (PRRs), like toll-like receptors (TLRs), sense microbial nucleic acids. This sensing is crucial in chronic inflammatory diseases, including oral conditions like periodontitis and cancer, offering therapeutic targets.
Area of Science:
- Immunology
- Molecular Biology
- Pathology
Background:
- Chronic inflammatory disorders involve complex host-pathogen interactions.
- Pattern Recognition Receptors (PRRs), particularly Toll-Like Receptors (TLRs), are key in sensing danger signals.
- Intracellular PRRs sensing nucleic acids have emerged as critical players in immunity and disease.
Purpose of the Study:
- To review advances in understanding how intracellular PRRs detect microbial nucleic acids.
- To explore the role of nucleic acid sensors in systemic diseases and oral pathologies.
- To highlight potential therapeutic strategies for disease prevention and treatment.
Main Methods:
- Literature review of current research on PRRs and nucleic acid sensing.
- Analysis of clinical and in vivo studies investigating PRR involvement in disease.
- Synthesis of findings on the link between oral inflammation and systemic conditions.
Main Results:
- Nucleic acid sensing by intracellular PRRs is implicated in diverse conditions including cancer, viral/bacterial infections, and autoimmune disorders.
- Overexpression of nucleic acid sensors is observed in diseased tissues, with knockout models showing altered disease progression.
- TLR9-mediated inflammation is linked to periodontal diseases, suggesting a connection between oral and systemic health.
Conclusions:
- Intracellular PRRs are central to sensing microbial nucleic acids and driving inflammatory responses.
- Nucleic acid sensing pathways represent a potential link between oral health and systemic diseases.
- Targeting nucleic acid sensors offers promising avenues for novel therapeutic interventions.
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