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.
Highlights
The family of cytolethal distending toxins (CDTs) consists of a number of bacterial protein exotoxins expressed by a broad range of Gram-negative bacteria, with a potential involvement in the pathogenesis of a diverse range of human infections
Aggregatibacter actinomycetemcomitans is a Gram-negative facultative anaerobe, which is highly implicated in the pathogenesis of localized aggressive periodontitis, a disease leading to tooth loss in adolescents or young adults
In other studies involving human intestinal epithelial cells, it was confirmed that infection with C. jejuni or just its outer membrane vesicles, was able to stimulate the production of pro-inflammatory IL-8, as well as the anti-inflammatory cytokine IL-10
Summary
The family of cytolethal distending toxins (CDTs) consists of a number of bacterial protein exotoxins expressed by a broad range of Gram-negative bacteria, with a potential involvement in the pathogenesis of a diverse range of human infections. They can be described as genotoxins, as their main action is to elicit DNA damage responses on the intoxicated host cells. The CdtA and CdtC subunits mediate the internalization of the CdtB subunit into the cell, which is a molecule functionally homologous to deoxyribonuclease I It is CdtB which is responsible for the induction of these deleterious effects on the host cells. It is the aim of this review to identify and present the current state of the literature with regards to the role of CDTs on host inflammatory responses, as well as the associated effects on bone remodeling
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