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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

The cytolethal distending toxin of Aggregatibacter actinomycetemcomitans inhibits macrophage phagocytosis and subverts cytokine production

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Author(s):
Ando-Suguimoto, Ellen Sayuri [1] ; da Silva, Maike Paulino [1] ; Kawamoto, Dione [1] ; Chen, Casey [2] ; DiRienzo, Joseph M. [3] ; Alves Mayer, Marcia Pinto [1]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, BR-05508900 Sao Paulo - Brazil
[2] Univ So Calif, Ostrow Sch Dent, Div Periodontol Diagnost Sci & Dent Hyg, Los Angeles, CA 90089 - USA
[3] Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 - USA
Total Affiliations: 3
Document type: Journal article
Source: CYTOKINE; v. 66, n. 1, p. 46-53, MAR 2014.
Web of Science Citations: 20
Abstract

Aggregatibacter actinomycetemcomitans is an important periodontal pathogen that can participate in periodontitis and other non-oral infections. The cytolethal distending toxin (Cdt) is among the virulence factors produced by this bacterium. The Cdt is also secreted by several mucosa-associated Gram-negative pathogens and may play a role in perpetuating the infection by modulating the immune response. Although the toxin targets a wide range of eukaryotic cell types little is known about its activity on macrophages which play a key part in alerting the rest of the immune system to the presence of pathogens and their virulence factors. In view of this, we tested the hypothesis that the A. actinomycetemcomitans Cdt (AaCdt) disrupts macrophage function by inhibiting phagocytic activity as well as affecting the production of cytokines. Murine macrophages were co-cultured with either wild-type A. actinomycetemcomitans or a Cdt(-) mutant. Viable counts and qPCR showed that phagocytosis of the wild-type strain was significantly reduced relative to that of the Cdt(-) mutant. Addition of recombinant Aa(r)Cdt to co-cultures along with the Cdt(-) mutant diminished the phagocytic activity similar to that observed with the wild type strain. High concentrations of Aa(r)Cdt resulted in decreased phagocytosis of fluorescent bioparticles. Nitric oxide production was modulated by the presence of Cdt and the levels of IL-1 beta, IL-12 and IL-10 were increased. Production of TNF-alpha did not differ in the co-culture assays but was increased by the presence of Aa(r)Cdt. These data suggest that the Cdt may modulate macrophage function in A. actinomycetemcomitans infected sites by impairing phagocytosis and modifying the pro-inflammatory/anti-inflammatory cytokine balance. (c) 2014 Elsevier Ltd. All rights reserved. (AU)