Down-regulation of NLRP3 inflammasome in gingival fibroblasts by subgingival biofilms: Involvement of Porphyromonas gingivalis

Abstract

Recognition of pathogen-associated molecular patterns that activate IL-1 is regulated by inflammasomes, predominantly of the nucleotide-binding oligomerization domain-like receptor (NLR) family. NLRP3 inflammasome is involved in the innate immune responses in periodontal disease. This is an inflammatory condition that destroys the tooth-supporting (periodontal) tissues, initiated by the subgingival formation of multi-species biofilms, frequently including the Gram-negative species Porphyromonas gingivalis. The aim of this study was to investigate the relative effect of P. gingivalis as part of subgingival biofilm, on the expressions of NLRP3 inflammasome, absent in melanoma (AIM)2 (a non-NLR inflammsome) and IL-1 by human gingival fibroblasts. The 10-species subgingival biofilm model, or its 9-species variant excluding P. gingivalis, were used to challenge the cells for 6 h. Gene expression analysis for various inflammasome components and IL-1 was performed by TaqMan real-time PCR. The 10-species subgingival biofilm reduced NLRP3 and IL-1, but did not affect AIM2 expression. Exclusion of P. gingivalis from the biofilm partially rescued NLRP3 and IL-1 expressions. In conclusion, subgingival biofilms down-regulate NLRP3 and IL-1 expression, partly because of P. gingivalis. These dampened host innate immune responses may favour the survival and persistence of the associated biofilm species in the periodontal tissues. expressions. In conclusion, subgingival biofilms down-regulate NLRP3 and IL-1β

Activation of NLRP3 and AIM2 Inflammasomes by Porphyromonas gingivalis Infection

“…In contrast to our findings, it was recently reported that NLRP3 expression is downregulated by subgingival biofilm in primary gingival fibroblast tissue, partly due to P. gingivalis (33). The discrepancy between studies may be attributed to the different cell types studied or to the difference between a live single-type bacterial infection and a biofilm infection.…”

Porphyromonas gingivalis Mediates Inflammasome Repression in Polymicrobial Cultures through a Novel Mechanism Involving Reduced Endocytosis

“…Additionally, our results rule out the possibility that P. gingivalis suppresses F. nucleatum-induced inflammasome activation through the reduction of endogenous levels of Nlrp3 or the other core components of its inflammasome. A recent study suggested that Nlrp3 is down-regulated by 33% in gingival fibroblast cultures colonized with a nine-species biofilm upon the inclusion of P. gingivalis (50). However, Il1b transcription was also reduced 35%, and it is therefore unclear whether reduced IL1b, rather than Nlrp3, may contribute to the reduced IL-1␤ secretion in that model.…”

<b><i>Porphyromonas gingivalis</i></b> Fimbriae Dampen P2X7-Dependent Interleukin-1β Secretion

“…The ability of P. gingivalis to stimulate the first but not the second signal may be a rare trait of periodontopathogens [17]. In addition, it is known that subgingival biofilms down-regulate NLRP3 and IL-1β gene expression in gingival fibroblasts in vitro , with P. gingivalis being a critical component of the biofilms [41]. The present literature supports the notion that, as part of the polymicrobial community, P. gingivalis can disrupt host-microbial homeostasis by dampening the pathogen-sensing capacity of the host cells via inflammasomes [42].…”