The capsule of Porphyromonas gingivalis reduces the immune response of human gingival fibroblasts

Abstract

BackgroundPeriodontitis is a bacterial infection of the periodontal tissues. The Gram-negative anaerobic bacterium Porphyromonas gingivalis is considered a major causative agent. One of the virulence factors of P. gingivalis is capsular polysaccharide (CPS). Non-encapsulated strains have been shown to be less virulent in mouse models than encapsulated strains.ResultsTo examine the role of the CPS in host-pathogen interactions we constructed an insertional isogenic P. gingivalis knockout in the epimerase-coding gene epsC that is located at the end of the CPS biosynthesis locus. This mutant was subsequently shown to be non-encapsulated. K1 capsule biosynthesis could be restored by in trans expression of an intact epsC gene. We used the epsC mutant, the W83 wild type strain and the complemented mutant to challenge human gingival fibroblasts to examine the immune response by quantification of IL-1β, IL-6 and IL-8 transcription levels. For each of the cytokines significantly higher expression levels were found when fibroblasts were challenged with the epsC mutant compared to those challenged with the W83 wild type, ranging from two times higher for IL-1β to five times higher for IL-8.ConclusionsThese experiments provide the first evidence that P. gingivalis CPS acts as an interface between the pathogen and the host that may reduce the host's pro-inflammatory immune response. The higher virulence of encapsulated strains may be caused by this phenomenon which enables the bacteria to evade the immune system.

The nucleoid-associated protein HUβ affects global gene expression in Porphyromonas gingivalis

“…The molecular mechanisms underlying iron uptake have been extensively studied (Olczak et al, 2005). Genes involved in iron acquisition include the hmuYRSTUV locus (PG1551-PG1556), which encodes a novel hybrid haemin-uptake system (Brunner et al, 2010;Lewis et al, 2006;Olczak et al, 2005Olczak et al, , 2008Simpson et al, 2000Simpson et al, , 2004Smalley et al, 2011); the hbp35 gene (PG0616), which encodes a haemin-binding protein that also exhibits thioredoxin activity (Hiratsuka et al, 2010;Shoji et al, 2010); the surface protein HusA (PG2227), which acts as a haemophore with very high affinity (Gao et al, 2010); the tlr (PG0644) iron transport locus Slakeski et al, 2000); the haemin-binding protein FetB (PG0669) and the surrounding genes in that locus; and PG0465, the ferric uptake regulator (fur) (Olczak et al, 2005). In addition, regulatory mechanisms controlling expression of iron acquisition genes have been identified, including the transcriptional activator encoded by PG1237, which has been shown to control expression of the hmu locus (Wu et al, 2009).…”

Subgingival Biofilm Structure

“…P. gingivalis strains on the other hand produce a capsular polysaccharide. Encapsulated strains have been shown to evade the immune system [45] but non-encapsulated strains are more adherent to epithelial cells and show strong autoaggregation and enhanced biofilm formation [46,47]. If and what type of free extracellular polysaccharide P. gingivalis produces for the formation of biofilms is unknown.…”

Mechanisms of Periodontitis - Induced Atherosclerosis

“…[41][42][43][44] Although many factors may influence the onset of periodontitis, periodontopathogen bacteria play a key role in the onset and severity of periodontal diseases. [42,45,46] PG is an anaerob obligat, [47] non-motile, [48] pleiomorphic bacteria, and posses a capsul. [49] PG shows a strong proteolitic activity, grows in anaerobic environment, and shows dark pigmentation (brown, dark green, or black) on blood agar.…”

“…[52] The capsul serves a protection to prevent it from phagocytosis 53 and triggers the secretion of IL-1, IL-6, dan IL-8. [48] The end products are various kinds of amino acid and endotoxin, haemolysin, collagenase and proteases which may damage immunoglobulins, complements, and hemesequestering proteins: a protein which inhibits collagenase activities. [42,53,54] PG was shown to be able to invade epithelium, [51] soft tissue, inhibit PMN cell migration across the epithelium [55] and may cause cytokine degradation in mammal cells.…”