Oral microbes and mucosal dendritic cells, “spark and flame” of local and distant inflammatory diseases

Mohamed M. Meghil, Christopher W. Cutler

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish (US)
Article number1643
JournalInternational journal of molecular sciences
Volume21
Issue number5
DOIs
StatePublished - Mar 2020

Keywords

  • Dendritic cells
  • Immunology
  • Periodontitis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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