Connection between Periodontitis-Induced Low-Grade Endotoxemia and Systemic Diseases: Neutrophils as Protagonists and Targets

Ljubomir Vitkov, Luis Munoz, Jasmin Knopf, Christine Schauer, Hannah Oberthaler, Bernd Minnich, Matthias Hannig*, Martin Hermann

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Periodontitis is considered a promoter ofmany systemic diseases, but the signaling pathways
of this interconnection remain elusive. Recently, it became evident that certain microbial challenges
promote a heightened response of myeloid cell populations to subsequent infections either with the
same or other pathogens. This phenomenon involves changes in the cell epigenetic and transcription,
and is referred to as “trained immunity”. It acts via modulation of hematopoietic stem and progenitor
cells (HSPCs). A main modulation driver is the sustained, persistent low-level transmission of
lipopolysaccharide from the periodontal pocket into the peripheral blood. Subsequently, the neutrophil
phenotype changes and neutrophils become hyper-responsive and prone to boosted formation of
neutrophil extracellular traps (NET). Cytotoxic neutrophil proteases and histones are responsible
for ulcer formations on the pocket epithelium, which foster bacteremia and endoxemia. The latter
promote systemic low-grade inflammation (SLGI), a precondition for many systemic diseases and
some of them, e.g., atherosclerosis, diabetes etc., can be triggered by SLGI alone. Either reverting the
polarized neutrophils back to the homeostatic state or attenuation of neutrophil hyper-responsiveness
in periodontitis might be an approach to diminish or even to prevent systemic diseases.
Original languageEnglish
Article number4647
Pages (from-to)1 - 17
Number of pages17
JournalInternational Journal of Molecular Sciences
Issue number9
Publication statusPublished - 28 Apr 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Copyright 2021 Elsevier B.V., All rights reserved.


  • Blood transmission of PAMPs
  • Loss of tolerance
  • Neutrophil hyper-responsiveness
  • Neutrophil-driven damages
  • Trained immunity
  • loss of tolerance
  • blood transmission of PAMPs
  • neutrophil hyper-responsiveness
  • neutrophil-driven damages
  • trained immunity

Fields of Science and Technology Classification 2012

  • 305 Other Human Medicine, Health Sciences

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