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Protective Effects against Brucella abortus 544 Infection in a Murine Macrophage Cell Line and in a Mouse Model via Treatment with Sirtuin 1 Activators Resveratrol, Piceatannol and Ginsenoside Rg3

  • Alisha Wehdnesday Bernardo Reyes (Department of Veterinary Paraclinical Sciences, College of Veterinary Medicine, University of the Philippines Los Banos) ;
  • Heejin Kim (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University) ;
  • Tran Xuan Ngoc Huy (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University) ;
  • Trang Thi Nguyen (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University) ;
  • Wongi Min (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University) ;
  • Hu Jang Lee (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University) ;
  • Jin Hur (College of Veterinary Medicine, Jeonbuk National University) ;
  • John Hwa Lee (College of Veterinary Medicine, Jeonbuk National University) ;
  • Suk Kim (Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University)
  • Received : 2022.09.19
  • Accepted : 2023.01.09
  • Published : 2023.04.28

Abstract

Brucellosis is a contagious zoonotic disease that infects millions of people annually with hundreds of millions more being exposed. It is caused by Brucella, a highly infectious bacterial species capable of infecting humans with an estimated dose of 10-100 organisms. Sirtuin 1 (SIRT1) has been reported to contribute to prevention of viral diseases as well as a chronic infection caused by Mycobacterium bovis. Here, we investigated the role of SIRT1 in the establishment of Brucella abortus infection in both in vitro and in vivo systems using the reported SIRT1 activators resveratrol (RES), piceatannol (PIC), and ginsenoside Rg3 (Rg3). In RAW264.7 cells, SIRT1 activators did not alter the adherence of Brucella or Salmonella Typhimurium. However, reduced uptake of Brucella was observed in cells treated with PIC and Rg3, and survival of Brucella within the cells was only observed to decrease in cells that were treated with Rg3, while PIC treatment reduced the intracellular survival of Salmonella. SIRT1 treatment in mice via oral route resulted in augmented Brucella resistance for PIC and Rg3, but not RES. PIC treatment favors Th2 immune response despite reduced serum pro-inflammatory cytokine production, while Rg3-treated mice displayed high IL-12 and IFN-γ serum production. Overall, our findings encourage further investigation into the complete mechanisms of action of the different SIRT1 activators used as well as their potential benefit as an effective alternative approach against intracellular and extracellular pathogens.

Keywords

Acknowledgement

This work was supported by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (IPET) through the Animal Disease Management Technology Development Program, funded by the Ministry of Agriculture, Food and Rural Affairs (122001021SB01061382116530000).

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