Neutrophil extracellular trap formation in supragingival biofilms

Hirschfeld, Josefine; Dommisch, Henrik; Skora, Philipp; Horváth, Gábor; Latz, Eicke; Hoerauf, Achim; Waller, Tobias; Kawai, Toshihisa; Jepsen, Søren; Deschner, James; Bekeredjian‐Ding, Isabelle

doi:10.1016/j.ijmm.2015.04.002

Cited by 56 publications

(52 citation statements)

References 80 publications

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“…Hirschfield et al reported NET formation was observed by a variety of oral bacteria, including S. gordonii, taken from supragingival biofilm and whole saliva samples in healthy donors (380). Similarly to the observations obtained with my data, S. gordonii challenge at MOI 10 produced ~10% NET formation (380).These results suggest that F. alocis may represent a unique species to the oral community, as NET formation is not observed.…”

Section: Discussionsupporting

confidence: 80%

“…In vivo observation of neutrophils revealed their presence in the dental plaque and that NET formation is detected in the oral biofilm, the saliva, and also the crevicular exudate (155,197,(380)(381)(382). Due to the large quantity of bacteria present dispersed throughout the gingival crevice, phagocytosis is an ineffective means for bacterial control, therefore NETs could serve as a more effective strategy for neutrophils to respond to infection (197).…”

Section: Discussionmentioning

confidence: 99%

“…If in the bloodstream, they could aid in spreading bacteria, however, if they are at the tissue-level, they may prevent adhesion and colonization of the host tissue by bacteria. There is also potential that NETs could also operate in a biofilm formation and overgrowth (380). This leads to the question of whether the presence of NETs may be of benefit to the host and limit disease progression or be detrimental to the host and further disease progression (155).…”

Section: Discussionmentioning

confidence: 99%

“…Through using patient studies, it will be possible to help determine what causes the inter-patient variability seen in NET formation and the impact this has on disease development and progression (380,403). Studies have suggested that NETs could be useful as predictors of disease development (170,404,405).…”

Section: Discussionmentioning

confidence: 99%

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Characterization of Filifactor alocis and its immune evasion strategies employed against human neutrophils.

Armstrong¹

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Characterization of Filifactor alocis and its immune evasion strategies employed against human neutrophils.

Armstrong¹

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“…Little is known about the differential interactions between oral bacteria and neutrophils; however, there is evidence that certain species and strains can evoke different neutrophil responses (13)(14)(15)(16). This study aimed to elucidate the ability of bacterial species and strains frequently isolated from the oral cavity of healthy and diseased individuals to activate ROS and NET responses in neutrophils.…”

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confidence: 99%

Modulation of Neutrophil Extracellular Trap and Reactive Oxygen Species Release by Periodontal Bacteria

et al. 2017

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Oral bacteria are the main trigger for the development of periodontitis, and some species are known to modulate neutrophil function. This study aimed to explore the release of neutrophil extracellular traps (NETs), associated antimicrobial proteins, and reactive oxygen species (ROS) in response to periodontal bacteria, as well as the underlying pathways. Isolated peripheral blood neutrophils were stimulated with 19 periodontal bacteria. NET and ROS release, as well as the expression of NET-bound antimicrobial proteins, elastase, myeloperoxidase, and cathepsin G, in response to these species was measured using fluorescence-based assays. NET and ROS release was monitored after the addition of NADP (NADPH) oxidase pathway modulators and inhibitors of Toll-like receptors (TLRs). Moreover, bacterial entrapment by NETs was visualized microscopically, and bacterial killing was assessed by bacterial culture. Certain microorganisms, e.g., Veillonella parvula and Streptococcus gordonii, stimulated higher levels of ROS and NET release than others. NETs were found to entrap, but not kill, all periodontal bacteria tested. NADPH oxidase pathway modulators decreased ROS production but not NET production in response to the bacteria. Interestingly, TLR inhibitors did not impact ROS and NET release. These data suggest that the variability in the neutrophil response toward different bacteria may contribute to the pathogenesis of periodontal diseases by mechanisms such as bacterial avoidance of host responses and activation of neutrophils. Moreover, our results indicate that bacterium-stimulated NET release may arise in part via NADPH oxidase-independent mechanisms. The role of TLR signaling in bacterium-induced ROS and NET release needs to be further elucidated.KEYWORDS neutrophils, NETs, reactive oxygen species, periodontitis, oral bacteria P eriodontitis is initiated by the accumulation of microbial biofilms at and below the gingival margin. Indeed, it has been estimated that ϳ700 oral bacterial species and ϳ1,200 predominant phylotypes exist (1-3). Of these bacterial species, 5 major bacterial complexes (red, orange, yellow, green, and purple) have been identified by Socransky et al. using DNA probes (4) and are referred to here as Socransky complexes. The clustering and ordination analysis allowed them to assign microbial species to a color complex on the basis of the strength of the association with each other and the clinical staging of periodontitis. The biofilms which develop during disease are orchestrated to maximize their adherence, communication, and survival. The accumulation of bacterial species within the biofilm enables its development and perseverance, and certain bacteria, such as Fusobacterium nucleatum, are key orchestrators of biofilm formation and maturation (5).In susceptible individuals, dysbiosis and an aberrant host-microbe equilibrium can result in the onset of disease (6), where the microbial biofilm thrives by exploiting the

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Correlations between different protein species of oral rinse MMP‐8 and patient‐related factors

Leppilahti,

Tervahartiala,

Kautiainen

et al. 2023

Clinical & Exp Dental Res

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ObjectivesThe aim of this study is to examine correlations between different oral rinse matrix metalloproteinase (MMP)‐8 protein species in western blot (WB) analysis, quantitative MMP‐8 measurements, and patient‐related factors. Elevated activated MMP‐8 (aMMP‐8) associate with periodontitis and a diagnostic point‐of‐care technology has been developed based on aMMP‐8. In WB, different MMP‐8 protein species can be analyzed. Relative abundancy of fragmented 20–25 kDa forms in WB has been associated with and reflects MMP‐8 activation and related fragmentation and elevated quantitative aMMP‐8 measurements.Material and MethodsA random sample of 192 participants from a periodontal disease screening study was used for this study. Oral rinse samples for biomarker analyses were collected before clinical periodontal examinations. aMMP‐8 immunofluorometric (IFMA) and WB analysis (utilizing the same monoclonal antibody, 8708), polymorphonuclear leukocyte (PMN) elastase activity test and tissue inhibitor of metalloproteinases (TIMP)‐1 ELISA levels were performed from the oral rinse samples. Distinct MMP‐8 protein species were differentiated in the WB analysis. Principal component (PC) analysis was conducted to explore correlation patterns between the different species. Adjusted correlation analysis between the extracted PCs of WB and aMMP‐8 IFMA levels and multilevel regression analysis were conducted to explore if the other periodontal disease‐related biomarkers and clinical surrogate measures and patient‐related factors are co‐variating with the extracted components.ResultsDistinct correlation patterns between the MMP‐8 protein species were observed. The first four PCs explained 89% of the whole variance in PC analysis. Statistically significant correlation (p < 0.05) were observed as follows: PC1 positively with 21 kDa (r = .69) and 25 kDa fragments (r = .55) and negatively with 150 kDa complexes (r = −.46). PC2 correlated with 45 (r = .70) and 55 kDa (r = .65) activated forms, PC3 with 70–80 kDa latent proforms (r = .63) and 90–100 kDa complexes (r = .67), and PC4 with 35 kDa fragments (r = .81). There were significant correlations between quantitative (IFMA) aMMP‐8 measurements and PC1 (p < 0.001), PC2 (<0.05) and PC3 (<0.05) but not with PC4. In multilevel regression models age, PMN elastase activity, TIMP‐1 levels, and a number of 4–5 mm periodontal pockets were associated with PC1, nonsmoking with PC2, age and PMN elastase activity with PC3, and age and smoking with PC4.ConclusionsRelative abundancy of fragmented 21–25 kDa protein species was correlated with the quantitative aMMP‐8 (IFMA) measurements, which is in line with previous results. Different patient‐related factors (smoking, age, proteolytic activity) may modify the formation of different MMP‐8 protein species in oral rinse samples and may cause variability in quantitative aMMP‐8 measurement.

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Neutrophil extracellular trap formation in supragingival biofilms

Cited by 56 publications

References 80 publications

Characterization of Filifactor alocis and its immune evasion strategies employed against human neutrophils.

Characterization of Filifactor alocis and its immune evasion strategies employed against human neutrophils.

Modulation of Neutrophil Extracellular Trap and Reactive Oxygen Species Release by Periodontal Bacteria

Correlations between different protein species of oral rinse MMP‐8 and patient‐related factors

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