Intracellular Growth Inhibition and Host Immune Modulation of 3-Amino-1,2,4-triazole in Murine Brucellosis

Int J Mol Sci. 2023 Dec 11;24(24):17352. doi: 10.3390/ijms242417352.

Abstract

Catalase, an antioxidant enzyme widely produced in mammalian cells and bacteria, is crucial to mitigating oxidative stress in hostile environments. This function enhances the intracellular survivability of various intracellular growth pathogens, including Brucella (B.) abortus. In this study, to determine whether the suppression of catalase can inhibit the intracellular growth of B. abortus, we employed 3-amino-1,2,4-triazole (3-AT), a catalase inhibitor, in both RAW 264.7 macrophage cells and an ICR mouse model during Brucella infection. The intracellular growth assay indicated that 3-AT exerts growth-inhibitory effects on B. abortus within macrophages. Moreover, it contributes to the accumulation of reactive oxygen species and the formation of nitric oxide. Notably, 3-AT diminishes the activation of the nucleus transcription factor (NF-κB) and modulates the cytokine secretion within infected cells. In our mouse model, the administration of 3-AT reduced the B. abortus proliferation within the spleens and livers of infected mice. This reduction was accompanied by a diminished immune response to infection, as indicated by the lowered levels of TNF-α, IL-6, and IL-10 and altered CD4+/CD8+ T-cell ratio. These results suggest the protective and immunomodulatory effects of 3-AT treatment against Brucella infection.

Keywords: 3-AT; Brucella abortus; ICR mouse; RAW 264.7 cell; catalase inhibitor; immune response; intracellular growth.

MeSH terms

  • Amitrole / pharmacology
  • Animals
  • Brucella abortus*
  • Brucellosis* / drug therapy
  • Brucellosis* / microbiology
  • Catalase
  • Immunity
  • Mammals
  • Mice
  • Mice, Inbred ICR

Substances

  • Amitrole
  • Catalase

Grants and funding

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).