Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 3 November 2023 / Approved: 3 November 2023 / Online: 3 November 2023 (05:07:39 CET)

A peer-reviewed article of this Preprint also exists.

Nguyen, T.T.; Huy, T.X.N.; Aguilar, C.N.T.; Reyes, A.W.B.; Salad, S.A.; Min, W.-G.; Lee, H.-J.; Kim, H.-J.; Lee, J.-H.; Kim, S. Intracellular Growth Inhibition and Host Immune Modulation of 3-Amino-1,2,4-triazole in Murine Brucellosis. Int. J. Mol. Sci. 2023, 24, 17352. Nguyen, T.T.; Huy, T.X.N.; Aguilar, C.N.T.; Reyes, A.W.B.; Salad, S.A.; Min, W.-G.; Lee, H.-J.; Kim, H.-J.; Lee, J.-H.; Kim, S. Intracellular Growth Inhibition and Host Immune Modulation of 3-Amino-1,2,4-triazole in Murine Brucellosis. Int. J. Mol. Sci. 2023, 24, 17352.

Abstract

Catalase, an antioxidant enzyme widely produced in mammalian cells and bacteria, is crucial in mitigating oxidative stress in a hostile environment. This function enhances the intracellular survivability of various intracellular growth pathogens, including Brucella abortus. In this study, to determine whether the inhibition of catalase can inhibit the intracellular growth of Brucella (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. Aside from that, 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 cytokine secretion within infected cells. In our mouse model, the administration of 3-AT reduced B. abortus proliferation within the spleen and liver of infected mice. This reduction was accompanied by a diminished immune response to infection, as indicated by lowered levels of TNF-α, IL-6, 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

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

Subject

Biology and Life Sciences, Immunology and Microbiology

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