Inflammatory and Bone Remodeling Responses to the Cytolethal Distending Toxins

Abstract

The cytolethal distending toxins (CDTs) are a family of exotoxins produced by a wide range of Gram-negative bacteria. They are known for causing genotoxic stress to the cell, resulting in growth arrest and eventually apoptotic cell death. Nevertheless, there is evidence that CDTs can also perturb the innate immune responses, by regulating inflammatory cytokine production and molecular mediators of bone remodeling in various cell types. These cellular and molecular events may in turn have an effect in enhancing local inflammation in diseases where CDT-producing bacteria are involved, such as Aggregatibacter actinomycetemcomitans, Haemophilus ducreyi, Campylobacter jejuni and Helicobacter hepaticus. One special example is the induction of pathological bone destruction in periodontitis. The opportunistic oral pathogen Aggregatibatcer actinoycemetemcomitans, which is involved in the aggressive form of the disease, can regulate the molecular mechanisms of bone remodeling in a manner that favors bone resorption, with the potential involvement of its CDT. The present review provides an overview of all known to-date inflammatory or bone remodeling responses of CDTs produced by various bacterial species, and discusses their potential contribution to the pathogenesis of the associated diseases.

Periodontopathogens and human β‐defensin‐2 expression in gingival crevicular fluid from patients with periodontal disease in Guangxi, China

“…A. actinomycetemcomitans is a gram‐negative facultative anaerobe, which is highly implicated in the pathogenesis of periodontitis. Although it is known that this species expresses two protein exotoxins, namely a leukotoxin and a cytolethal distending toxin, the capacity of A. actinomycetemcomitans to regulate the immune response is not evident . Vankeerberghen et al .…”

“…A. actinomycetemcomitans is a gram-negative facultative anaerobe, which is highly implicated in the pathogenesis of periodontitis. Although it is known that this species expresses two protein exotoxins, namely a leukotoxin and a cytolethal distending toxin, the capacity of A. actinomycetemcomitans to regulate the immune response is not evident (32 (36) observed that human gingival epithelial cells expressed hBD-2 when exposed to A. actinomycetemcomitans. Mintz et al (37) confirmed a competitive mechanism by which A. actinomycetemcomitans induced or inhibited the expression of hBD-2.…”

Virulence and Pathogenicity Properties of Aggregatibacter actinomycetemcomitans

“…Another potentially pathogenic mechanisms activated by CDT is the stimulation of pro-inflammatory and osteolytic cytokine production by the intoxicated host cells [86]. It has been shown that CDT can stimulate the production of pro-inflammatory cytokines by peripheral blood mononuclear cells, such as interferon (IFN)-γ, Interleukin (IL)-1β, IL-6, and IL-8, a virulence property potentially independent of the toxin's deoxyribonuclease I activity [85].…”

Establishment of an oral infection model resembling the periodontal pocket in a perfusion bioreactor system

“…3 Besides, recent evidence shows that the effects of periodontal infections may well expand beyond the oral cavity, to be implicated in systemic diseases, such as diabetes mellitus and cardiovascular diseases. 4,5 The causation of these infections involves the complex interaction between biofilm communities forming on the tooth surface, and the neighboring host periodontal tissues. 6 Biofilms are polymicrobial communities embedded in a dense extracellular matrix produced by the different constituent species.…”