Humoral immune response to Aggregatibacter actinomycetemcomitans leukotoxin

Brage, Monica; Holmlund, Anders; Johansson, Anders

doi:10.1111/j.1600-0765.2010.01325.x

Cited by 29 publications

(44 citation statements)

References 38 publications

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“…The serum was a commercial product that was pooled from many human donors, and a large proportion of individuals with periodontitis express antibodies against whole A. actinomycetemcomitans as well as A. actinomycetemcomitans leukotoxin. 31 Although it is likely that these antibodies produced similar effects on bacterial killing by the two antibiotics used in this study, it would have been useful to characterize the levels of antibodies in the serum.…”

Section: Discussionmentioning

confidence: 99%

Azithromycin Enhances Phagocytic Killing of Aggregatibacter actinomycetemcomitans Y4 by Human Neutrophils

Lai

Schibler

Walters

2015

Journal of Periodontology

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Background Aggregatibacter actinomycetemcomitans resists killing by neutrophils and is inhibited by azithromycin (AZM) and amoxicillin (AMX). AZM actively concentrates inside host cells, whereas AMX enters by diffusion. The present study is conducted to determine whether AZM is more effective than AMX at enhancing phagocytic killing of A. actinomycetemcomitans by neutrophils. Methods Killing assays were conducted in the presence of either 2 μg/mL AZM or 16 μg/mL AMX (equipotent against A. actinomycetemcomitans). Neutrophils were loaded by incubation with the appropriate antibiotic. Opsonized A. actinomycetemcomitans strain Y4 was incubated with the indicated antibiotic alone, with loaded neutrophils and antibiotic, or with control neutrophils (without antibiotic) at multiplicities of infection (MOIs) of 30 and 90 bacteria per neutrophil. Results Neutrophil incubation with 2 μg/mL AZM yielded an intracellular concentration of 10 μg/mL. At an MOI of 30, neutrophils loaded with AZM failed to kill significantly more bacteria than control neutrophils during the 60- and 90-minute assay periods. At an MOI of 90, neutrophils loaded with AZM killed significantly more bacteria than either AZM alone or control neutrophils during 60- and 90-minute incubations (P <0.05), and killed significantly more bacteria after 90 minutes than the sum of the killing produced by AZM alone or neutrophils alone. Neutrophils incubated with AMX under identical conditions also killed significantly more bacteria than either AMX alone or control neutrophils, but there was no evidence of synergism between AMX and neutrophils. Conclusions Neutrophils possess a concentrative transport system for AZM that may enhance killing of A. actinomycetemcomitans. Its effects are most pronounced when neutrophils are greatly outnumbered by bacteria.

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Section: Discussionmentioning

confidence: 99%

Azithromycin Enhances Phagocytic Killing of Aggregatibacter actinomycetemcomitans Y4 by Human Neutrophils

Lai

Schibler

Walters

2015

Journal of Periodontology

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“…79,80 It has also been shown that systemic antibodies against LtxA efficiently neutralize the activity of the toxin, which might interfere with the pathogenicity of A. actinomycetemcomitans, both locally and systemically. 81 As described in detail above, LtxA induces a massive secretion of bioactive IL-1b from macrophages. Interestingly, a receptor protein for this cytokine with regulatory properties has been identified on A. actinomyctemcomitans, which indicates further interactions with the host inflammatory response.…”

Section: A Actinomycetemcomitans In the Complex Biofilm Of The Periomentioning

confidence: 92%

Aggregatibacter actinomycetemcomitans: Virulence of its leukotoxin and association with aggressive periodontitis

2014

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“…Whether the expressed and exported LtxA remains associated with the bacterial outer membrane or is secreted into the environment is a topic of controversy, and the mechanisms that keep the toxin associated with the membrane are still not fully understood. However, the serum-mediated release of the toxin (144, 145), as well as its highly systemic immunogenic response (146), indicate a substantial release of the toxin from bacteria growing in an oral biofilm in vivo .…”

Section: Leukotoxinmentioning

confidence: 99%

“…More recently, T-regulatory (Treg) and Th17 cells have been detected in periodontal tissues indicating that these cells are also important in the host response and pathogenesis of periodontal disease (168). The strong acquired systemic humoral immune response induced by LtxA indicates direct contact between this molecule and cells of lymphoid origin (146, 169). The ability of LtxA to induce apoptosis in lymphocytes might contribute to a locally impaired acquired immune response in periodontal infections.…”

Section: Leukotoxinmentioning

confidence: 99%

“…The highly systemic immunogenic host response against LtxA of A. actinomycetemcomitans -infected subjects indicates that direct contact between the antigen-presenting macrophages and LtxA occurs (146, 169). The enhanced LtxA sensitivity of human macrophages indicates that these antigen-presenting cells might be affected during a primary infection with leukotoxic A. actinomycetemcomitans , which might cause a delayed acquired immune response.…”

Section: Leukotoxinmentioning

confidence: 99%

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Pathogenicity of the highly leukotoxic JP2 clone ofAggregatibacter actinomycetemcomitansand its geographic dissemination and role in aggressive periodontitis

Haubek

Johansson

2014

Journal of Oral Microbiology

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For decades, Aggregatibacter actinomycetemcomitans has been associated with aggressive forms of periodontitis in adolescents. In the middle of the 1990s, a specific JP2 clone of A. actinomycetemcomitans, belonging to the cluster of serotype b strains of A. actinomycetemcomitans and having a number of other characteristics, was found to be strongly associated with aggressive forms of periodontitis, particularly in North Africa. Although several longitudinal studies still point to the bacterial species, A. actinomycetemcomitans as a risk factor of aggressive periodontitis, it is now also widely accepted that the highly leukotoxic JP2 clone of A. actinomycetemcomitans is implicated in rapidly progressing forms of aggressive periodontitis. The JP2 clone strains are highly prevalent in human populations living in Northern and Western parts of Africa. These strains are also prevalent in geographically widespread populations that have originated from the Northwest Africa. Only sporadic signs of a dissemination of the JP2 clone strains to non-African populations have been found despite Africans living geographically widespread for hundreds of years. It remains an unanswered question if a particular host tropism exists as a possible explanation for the frequent colonization of the Northwest African population with the JP2 clone. Two exotoxins of A. actinomycetemcomitans are known, leukotoxin (LtxA) and cytolethal distending toxin (Cdt). LtxA is able to kill human immune cells, and Cdt can block cell cycle progression in eukaryotic cells and thus induce cell cycle arrest. Whereas the leukotoxin production is enhanced in JP2 clone strains thus increasing the virulence potential of A. actinomycetemcomitans, it has not been possible so far to demonstrate such a role for Cdt. Lines of evidence have led to the understanding of the highly leukotoxic JP2 clone of A. actinomycetemcomitans as an aetiological factor of aggressive periodontitis. Patients, who are colonized with the JP2 clone, are likely to share this clone with several family members because the clone is transmitted through close contacts. This is a challenge to the clinicians. The patients need intense monitoring of their periodontal status as the risk for developing severely progressing periodontal lesions are relatively high. Furthermore, timely periodontal treatment, in some cases including periodontal surgery supplemented by the use of antibiotics, is warranted. Preferably, periodontal attachment loss should be prevented by early detection of the JP2 clone of A. actinomycetemcomitans by microbial diagnostic testing and/or by preventive means.

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Humoral immune response to Aggregatibacter actinomycetemcomitans leukotoxin

Abstract: Systemic antibodies against A. actionmycetemcomitans leukotoxin were common in this adult Swedish population. These antibodies might contribute to limit the systemic effects of the infection.

Cited by 29 publications

References 38 publications

Azithromycin Enhances Phagocytic Killing of Aggregatibacter actinomycetemcomitans Y4 by Human Neutrophils

Azithromycin Enhances Phagocytic Killing of Aggregatibacter actinomycetemcomitans Y4 by Human Neutrophils

Aggregatibacter actinomycetemcomitans: Virulence of its leukotoxin and association with aggressive periodontitis

Pathogenicity of the highly leukotoxic JP2 clone ofAggregatibacter actinomycetemcomitansand its geographic dissemination and role in aggressive periodontitis

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