2 research outputs found
Connection between Periodontitis-Induced Low-Grade Endotoxemia and Systemic Diseases: Neutrophils as Protagonists and Targets
Periodontitis is considered a promoter of many 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
Breaking the Gingival Barrier in Periodontitis
The break of the epithelial barrier of gingiva has been a subject of minor interest, albeit
playing a key role in periodontal pathology, transitory bacteraemia, and subsequent systemic lowgrade inflammation (LGI). The significance of mechanically induced bacterial translocation in gingiva
(e.g., via mastication and teeth brushing) has been disregarded despite the accumulated knowledge of
mechanical force effects on tight junctions (TJs) and subsequent pathology in other epithelial tissues.
Transitory bacteraemia is observed as a rule in gingival inflammation, but is rarely observed in
clinically healthy gingiva. This implies that TJs of inflamed gingiva deteriorate, e.g., via a surplus of
lipopolysaccharide (LPS), bacterial proteases, toxins, Oncostatin M (OSM), and neutrophil proteases.
The inflammation-deteriorated gingival TJs rupture when exposed to physiological mechanical forces.
This rupture is characterised by bacteraemia during and briefly after mastication and teeth brushing,
i.e., it appears to be a dynamic process of short duration, endowed with quick repair mechanisms. In
this review, we consider the bacterial, immune, and mechanical factors responsible for the increased
permeability and break of the epithelial barrier of inflamed gingiva and the subsequent translocation
of both viable bacteria and bacterial LPS during physiological mechanical forces, such as mastication
and teeth brushing