Periodontal pathogen peptidoglycan scavenging regulates Inflammation via NOD2 modulation

Abstract

It is well recognized that the periodontal pathogen Tannerella forsythia is unable to de novo synthesize the amino sugars required for building its peptidoglycan backbone (PGN; cell-wall). Therefore, to survive in its subgingival niche, the bacterium recycles the peptidoglycan fragments released by the cohabiting bacteria during their cell-wall turnover in the process of cell division. The current study was designed to assess the potential impact of this peptidoglycan scavenging by T. forsythia on gingival inflammation. PGN fragments have a strong inflammtory potential in the host tissues, as they act as inducers of inflammatory NOD2 receptor (nucleotide-binding oligomerization domain-containing protein 2). To test this hypothesis, a simplified in vitro coculture model was developed in which Fusobacterium nucleatum, a cohabiting bacterium of the subgingival biofilm plaque, acted as a PGN donor with T. forsythia as the scavenger of PGN. After coculture incubations, the inflammatory potential of the spent medium was assayed with a reporter cell line for NOD2. The results as presented here showed that the wild-type T. forsythia strain, by successfully scavenging the PGN fragments (NOD2 ligand), dampened the inflammatory potential of the spent coculture medium when compared to the inflammatory potential of the spent medium from the F. nucleatum alone or the spent medium from the cocultures of F. nucleatum with a mutant of T. forsythia deficient in the expression of anhydromuropeptide (AmpG) permease involved in PGN uptake. Taken together, these studies support the notion that in the in vivo setting T. forsythia, by scavenging PGN, might dampen the NOD2-mediated inflammatory response and thus modulate the inflammatory environment of the gingival niche.