Analysis of cytolethal distending toxin (CDT) effect in inflammasome activation

• Grant number: 12/05887-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: October 15, 2012
• End date: April 14, 2013
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Marcia Pinto Alves Mayer
• Grantee: Ellen Sayuri Ando Suguimoto
• Supervisor: Denis F. Kinane
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Pennsylvania, United States

Abstract

Aggregatibacter actinomycetemcomitans is an important periodontal pathogen associated with periodontal diseases and extra-oral infections as endocarditis. A. actinomycetemcomitans has the ability to adhere and invade and epithelial cells, and to survive and perpetuate in infected tissues, produces many virulence factors, including the cytolethal distending toxin (Cdt). In our previous results, AaCdt seems to act as a modulator of the immune response of macrophages, increasing the production of proinflamatory cytokines such as IL-1² and IL-12 and in the other hand, decreasing the nitric oxide production. Cdt is produced by several Gram - negative pathogens. Recently, a multiprotein complex called inflammasome was discovered and its activation leads to production of IL-1² and IL-18 by infected cells.The inflammasome is present in Gram-negative pathogens and it is activated in the presence of internalized bacteria and its antigens. Objective: Determine the Cdt activity in the inflammasome activation in gingival epithelial cells, macrophages and dendritic cells. Methods: Human gingival epithelial cell, macrophages and dendritic cells will be challenge with different concentrations of purified recombinant Cdt activated or not with LPS from A. actinomycetemcomitans. The activation of inflammosome pathway will be detected by quantitative PCR and ELISA assay and NO production. To confirm the pathway of activation, silencing of iRNA and phosporylation assays will be performed. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ANDO-SUGUIMOTO, ELLEN S.; BENAKANAKERE, MANJUNATHA R.; MAYER, MARCIA P. A.; KINANE, DENIS F.. Distinct Signaling Pathways Between Human Macrophages and Primary Gingival Epithelial Cells by Aggregatibacter actinomycetemcomitans. PATHOGENS, v. 9, n. 4, APR 2020. (12/05887-0, 15/18273-9)