Characterization and serotype distribution of Aggregatibacter actinomycetemcomitans isolated from a population of periodontitis patients in Spain

Mínguez, María José Aparicio; Pousa, Xiana; Herrera, David; Blasi, A; Sánchez, Mari Carmen; León, Rubén; Sanz, Mariano

doi:10.1016/j.archoralbio.2014.07.021

Cited by 33 publications

(29 citation statements)

References 57 publications

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“…Although Aa has historically been linked to localized aggressive periodontitis (LAP) in adolescents (25), more recent evidence suggests a previously underappreciated role in chronic periodontitis (26-28). Indeed, we confirmed exposure to Aa LtxA in 62% (68/109) of individuals with chronic periodontitis by ELISA (62% vs 11% of controls; p<0.0001) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Aggregatibacter actinomycetemcomitans –induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis

et al. 2016

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A bacterial etiology of rheumatoid arthritis (RA) has been suspected since the beginnings of modern germ theory. Recent studies implicate mucosal surfaces as sites of disease initiation. The common occurrence of periodontal dysbiosis in RA suggests that oral pathogens may trigger the production of disease-specific autoantibodies and arthritis in susceptible individuals. We used mass spectrometry to define the microbial composition and antigenic repertoire of gingival crevicular fluid in patients with periodontal disease and healthy controls. Periodontitis was characterized by the presence of citrullinated autoantigens that are primary immune targets in RA. The citrullinome in periodontitis mirrored patterns of hypercitrullination observed in the rheumatoid joint, implicating this mucosal site in RA pathogenesis. Proteomic signatures of several microbial species were detected in hypercitrullinated periodontitis samples. Among these, Aggregatibacter actinomycetemcomitans (Aa), but not other candidate pathogens, induced hypercitrullination in host neutrophils. We identified the pore-forming toxin leukotoxin-A (LtxA) as the molecular mechanism by which Aa triggers dysregulated activation of citrullinating enzymes in neutrophils, mimicking membranolytic pathways that sustain autoantigen citrullination in the RA joint. Moreover, LtxA induced changes in neutrophil morphology mimicking extracellular trap formation, thereby releasing the hypercitrullinated cargo. Exposure to leukotoxic Aa strains was confirmed in patients with RA and was associated with both anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF). The effect of HLA-DRB1 shared epitope alleles on autoantibody positivity was limited to RA patients that were exposed to Aa. These studies identify the periodontal pathogen Aa as a candidate bacterial trigger of autoimmunity in RA.

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Section: Resultsmentioning

confidence: 99%

Aggregatibacter actinomycetemcomitans –induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis

et al. 2016

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“…[34][35][36] Therefore, elimination or removal of the periodontal pocket epithelium plays an essential goal in the treatment of CP by allowing a better connective tissue formation. In a histologic study on pig models, Romanos et al 20 demonstrated that treatment of periodontal tissues with a 980 nm diode laser completely removes the epithelium in periodontal pockets as compared with conventional treatment with hand instruments.…”

Section: Discussionmentioning

confidence: 99%

Role of Diode Lasers (800–980 Nm) as Adjuncts to Scaling and Root Planing in the Treatment of Chronic Periodontitis: A Systematic Review

Qadri

Javed

Johannsen

et al. 2015

Photomedicine and Laser Surgery

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“…Co‐infection with two or three different serotypes affects up to one‐third of periodontitis patients positive for A. actinomycetemcomitans (Minguez et al, ; van der Reijden, Bosch‐Tijhof, Velden, & Winkelhoff, ; Roman‐Torres et al, ; Rylev & Kilian, ; Saarela et al, ). Therefore, in this study the production of IFN‐γ, CRP, MMP‐2, and MMP‐9 by DCs co‐infected with different combinations of the A. actinomycetemcomitans serotypes was also analyzed.…”

Section: Discussionmentioning

confidence: 99%

“…These A. actinomycetemcomitans serotypes differ in their ability to induce response in host immune cells; in particular, serotype b induces higher levels of Th1 and Th17 types of cytokines in DCs compared with the other serotypes (Díaz‐Zúñiga, Monasterio, et al, ; Díaz‐Zúñiga et al, ). Interestingly, although most of the periodontitis patients being positive for A. actinomycetemcomitans harbor only one serotype within the subgingival biofilm, several studies have reported that 15%–33% of these patients harbor two or three different A. actinomycetemcomitans serotypes in the same sampled periodontal pocket (Minguez et al, ; Roman‐Torres et al, ; Rylev & Kilian, ; Saarela et al, 1992; van der Reijden, Bosch‐Tijhof, van der Velden, & van Winkelhoff, ). In these cases, the serotype diversity of A. actinomycetemcomitans within periodontal lesions could lead to a modification of their virulence on immune cells that infiltrate the infected periodontal tissues.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of serotype a of Aggregatibacter actinomycetemcomitans on the increased destructive potential of serotype b

et al. 2019

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Objective The serotype b of Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) induces higher cytokine production in dendritic cells (DCs) compared with the other serotypes. However, this increased immunostimulatory potential was modified when DCs were co‐infected with the other A. actinomycetemcomitans serotypes. This study aimed to analyze whether the production of interferon gamma (IFN‐γ), C‐reactive protein (CRP), matrix metalloproteinase (MMP)‐2, and MMP‐9, as well as the activity of osteoclasts, also varies when DCs are co‐infected with the A. actinomycetemcomitans serotypes. Materials and Methods Human DCs were stimulated with the A. actinomycetemcomitans serotypes using the following stimulatory conditions: serotype a/b/c/a+b/a+c/b+c/a+b+c. The IFN‐γ, CRP, and MMP‐2 levels were quantified by ELISA. The active form of MMP‐9 was quantified using fluorescent functional assays. The MMP‐2 gelatinolytic activity was identified by zymogram. The osteoclast activity was determined by quantifying the TRAP expression and resorption‐pit formation using cytochemistry and osteoassays. Results Higher levels of IFN‐γ, CRP, MMP‐2, MMP‐9, and osteoclast activity were detected when DCs were stimulated with the serotype b of A. actinomycetemcomitans compared with the others. This increased immunostimulatory potential attributed to serotype b diminished when DCs were co‐infected with the serotype a. Conclusions This study provides new insights into the virulence of A. actinomycetemcomitans and reveals important differences in the immunostimulatory and pro‐destructive potential among its serotypes.

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Characterization and serotype distribution of Aggregatibacter actinomycetemcomitans isolated from a population of periodontitis patients in Spain

Cited by 33 publications

References 57 publications

Aggregatibacter actinomycetemcomitans –induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis

Aggregatibacter actinomycetemcomitans –induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis

Role of Diode Lasers (800–980 Nm) as Adjuncts to Scaling and Root Planing in the Treatment of Chronic Periodontitis: A Systematic Review

Inhibitory effect of serotype a of Aggregatibacter actinomycetemcomitans on the increased destructive potential of serotype b

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