The Regulatory Effect of Coaggregation Between Fusobacterium nucleatum and Streptococcus gordonii on the Synergistic Virulence to Human Gingival Epithelial Cells

Abstract

In subgingival plaque biofilms, Fusobacterium nucleatum is closely related to the occurrence and development of periodontitis. Streptococcus gordonii, as an accessory pathogen, can coaggregate with periodontal pathogens, facilitating the subgingival colonization of periodontal pathogens. Studies have shown that F. nucleatum can coaggregate with S. gordonii and colonize the subgingival plaque. However, most studies have focused on monocultures or coinfection of species and the potential impact of coaggregation between the two species on periodontal interactions to human gingival epithelial cells (hGECs) remains poorly understood. The present study explored the effect of coaggregation between F. nucleatum and S. gordonii on subgingival synergistic virulence to hGECs. The results showed that coaggregation inhibited the adhesion and invasion of F. nucleatum to hGECs compared with that in the F. nucleatum monoculture and coinfection group. Coaggregation and coinfection with F. nucleatum both enhanced S. gordonii adhesion to hGECs, but neither of the two groups affected S. gordonii invasion to hGECs compared with S. gordonii monoculture. The gene expression levels of TLR2 and TLR4 in hGECs in the coaggregation group were higher than those in the monoculture groups but lower than those in the coinfection group. Compared with coinfection, the coaggregation inhibited apoptosis of hGECs and promoted the secretion of the proinflammatory cytokines TNF-α and IL-6 by hGECs, showed a synergistic inflammatory effect, while coaggregation inhibited the secretion of the anti-inflammatory cytokine TGF-β1. Coaggregation enhanced the phosphorylation of p65, p38, and JNK proteins and therefore activated the NF-κB and MAPK signaling pathways. Pretreatment with a pathway antagonist/inhibitor decreased the phosphorylation levels of proteins and the secretion of TNF-α and IL-6. In conclusion, coaggregation inhibited the adhesion and invasion of F. nucleatum to hGECs. However, it enhanced the adhesion of S. gordonii to hGECs. Compared with coinfection, coaggregation inhibited the apoptosis of hGECs. The coaggregation coordinately promoted the secretion of TNF-α and IL-6 by hGECs through the TLR/NF-κB and TLR/MAPK signaling pathways while inhibiting the secretion of TGF-β1, thus aggravating the inflammatory response of hGECs.

Coaggregated E. faecalis with F. nucleatum regulated environmental stress responses and inflammatory effects

“…Our previous study reported that the pro-inflammatory factors IL-1β and IL-6 secreted by macrophages were markedly reduced following the coaggregated S. gordonii and Fnp infection (Liu et al 2021 ). Another article of our group found that compared with coculture of species, the coaggregated S. gordonii and Fnp enhanced proinflammatory cytokines TNF-α and IL-6 production by human gingival epithelial cells (hGECs) (Yang et al 2022 ). These results also suggested that the immunoregulatory properties of interspecies interaction might be host cell-specific, since coaggregation between S. gordonii and Fnp exerted pro-inflammatory effects on HGECs but anti-inflammatory roles on macrophages (Liu et al 2021 ; Yang et al 2022 ).…”

“…Another article of our group found that compared with coculture of species, the coaggregated S. gordonii and Fnp enhanced proinflammatory cytokines TNF-α and IL-6 production by human gingival epithelial cells (hGECs) (Yang et al 2022 ). These results also suggested that the immunoregulatory properties of interspecies interaction might be host cell-specific, since coaggregation between S. gordonii and Fnp exerted pro-inflammatory effects on HGECs but anti-inflammatory roles on macrophages (Liu et al 2021 ; Yang et al 2022 ). In this study, the coaggregation of Ef and Fnp dramatically decreased the levels of pro-inflammatory cytokines IL-6, TNF-α, and chemokine MCP-1 secreted by macrophages.…”

“…50 nM phorbol 12-myristate 13-acetate (PMA, Sigma, USA) was utilized to obtain THP-1-derived macrophages (dTHP-1 cells). The dTHP-1 cells infection models by different forms of bacterial (monospecies, coaggregated Ef-Fnp, and coculture Ef + Fnp) were established at a multiplicity of infection (MOI, bacteria: dTHP-1 cells) of 10 as described previously (Liu et al 2021 ; Yang et al 2022 ). The bacterial volumes of the coaggregates, monoculture and coculture were adjusted to reach a similar number of CFUs.…”

TCPP/MgO-loaded PLGA microspheres combining photodynamic antibacterial therapy with PBM-assisted fibroblast activation to treat periodontitis

“…1,42 S. gordonii can also co-aggregate with F. nucleatum, facilitating its colonization in the subgingival plaque and aggravating the inflammatory response of human gingival epithelial cells. 43 Fig. 3a shows the agar plate images of P. gingivalis, F. nucleatum and S. gordonii.…”

Ebselen Optimized the Therapeutic Effects of Silver Nanoparticles for Periodontal Treatment

“… 1 Streptococcus gordonii ( S. gordonii ) is an early colonizer that can easily attach to the tooth surfaces and facilitate the colonization of other periodontal pathogens to establish subgingival biofilms. 2 , 3 Fusobacterium nucleatum ( F. nucleatum ) can act as a bridge pathogen between the early and late colonizers by creating favorable conditions for the outgrowth of the late colonizer, such as Porphyromonas gingivalis ( P. gingivalis ), which is a keystone pathogen in the etiology of chronic periodontitis. 4 P. gingivalis can invade cells and tissues where they can maintain viability to avoid immune surveillance, thus easily developing antibiotic resistance and producing persistent infection.…”