Oral Microbes and Mucosal Dendritic Cells, "Spark and Flame" of Local and Distant Inflammatory Diseases.
Mohamed M MeghilChristopher W CutlerPublished in: International journal of molecular sciences (2020)
Mucosal health and disease is mediated by a complex interplay between the microbiota ("spark") and the inflammatory response ("flame"). Pathobionts, a specific class of microbes, exemplified by the oral microbe Porphyromonas gingivalis, live mostly "under the radar" in their human hosts, in a cooperative relationship with the indigenous microbiota. Dendritic cells (DCs), mucosal immune sentinels, often remain undisturbed by such microbes and do not alert adaptive immunity to danger. At a certain tipping point of inflammation, an "awakening" of pathobionts occurs, wherein their active growth and virulence are stimulated, leading to a dysbiosis. Pathobiont becomes pathogen, and commensal becomes accessory pathogen. The local inflammatory outcome is the Th17-mediated degenerative bone disease, periodontitis (PD). In systemic circulation of PD subjects, inflammatory DCs expand, carrying an oral microbiome and promoting Treg and Th17 responses. At distant peripheral sites, comorbid diseases including atherosclerosis, Alzheimer's disease, macular degeneration, chronic kidney disease, and others are reportedly induced. This review will review the immunobiology of DCs, examine the complex interplay of microbes and DCs in the pathogenesis of PD and its comorbid inflammatory diseases, and discuss the role of apoptosis and autophagy in this regard. Overall, the pathophysiological mechanisms of DC-mediated chronic inflammation and tissue destruction will be summarized.
Keyphrases
- oxidative stress
- dendritic cells
- diabetic rats
- inflammatory response
- chronic kidney disease
- immune response
- cell death
- healthcare
- endothelial cells
- ulcerative colitis
- public health
- regulatory t cells
- pseudomonas aeruginosa
- lymph node
- staphylococcus aureus
- optical coherence tomography
- end stage renal disease
- mental health
- bone mineral density
- cognitive decline
- type diabetes
- drug induced
- cystic fibrosis
- lipopolysaccharide induced
- body composition
- biofilm formation
- risk assessment
- diabetic retinopathy
- health information
- high glucose
- bone regeneration
- clinical decision support
- tandem mass spectrometry
- mild cognitive impairment
- human health