An analysis of the implication of the PD-1/PD-L1 immune checkpoint in
periodontitis is provided with the objective to propose a novel therapeutic approach. An exhaustive survey of the literature has been performed to answer two questions: (1) Is there a role for PD-1 and/or PD-L1 in the development of
periodontitis? (2) Which natural products interfere with the checkpoint activity and show activity against
periodontitis? All online published information was collected and analyzed. The pathogenic bacteria Porphyromonas gingivalis, through its membrane-attached peptidoglycans, exploits the PD-1/PD-L1 checkpoint to evade immune response and to amplify the
infection. Three anti-inflammatory natural products (and derivatives or
plant extracts) active against
periodontitis and able to interfere with the checkpoint were identified. Both
curcumin and
baicalin attenuate
periodontitis and induce a down-regulation of PD-L1 in cells. The
terpenoid saponin platycodin D inhibits the growth of P. gingivalis responsible for
periodontitis and shows a rare capacity to induce the extracellular release of a soluble form of PD-L1, thereby restoring T cell activation. A potential PD-L1 shedding mechanism is discussed. The targeting of the PD-1/PD-L1 immune checkpoint could be considered a suitable approach to improve the treatment of
chronic periodontitis. The plant natural products
curcumin,
baicalin and
platycodin D should be further evaluated as PD-1/PD-L1 checkpoint modulators active against
periodontitis.