Imipramine-induced immunomodulation and intracellular growth inhibition during Brucella abortus 544 infection in RAW 264.7 cells and BALB/c mice

Brucellosis is a significant zoonotic infection with increasing global prevalence. Traditional treatments rely on antibiotic combinations, but challenges such as drug resistance and relapse necessitate the exploration of alternative therapeutic options. Imipramine hydrochloride (ImiP) has shown pote...

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Main Authors: Ched Nicole Turbela Aguilar, Tran Xuan Ngoc Huy, Trang Thi Nguyen, Said Abdi Salad, Seong Eun Cho, Il-Hwa Hong, Wongi Min, Hu Jang Lee, Suk Kim
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Veterinary Science
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Online Access:https://www.frontiersin.org/articles/10.3389/fvets.2025.1598106/full
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author Ched Nicole Turbela Aguilar
Tran Xuan Ngoc Huy
Trang Thi Nguyen
Said Abdi Salad
Seong Eun Cho
Il-Hwa Hong
Wongi Min
Hu Jang Lee
Suk Kim
author_facet Ched Nicole Turbela Aguilar
Tran Xuan Ngoc Huy
Trang Thi Nguyen
Said Abdi Salad
Seong Eun Cho
Il-Hwa Hong
Wongi Min
Hu Jang Lee
Suk Kim
author_sort Ched Nicole Turbela Aguilar
collection DOAJ
description Brucellosis is a significant zoonotic infection with increasing global prevalence. Traditional treatments rely on antibiotic combinations, but challenges such as drug resistance and relapse necessitate the exploration of alternative therapeutic options. Imipramine hydrochloride (ImiP) has shown potential as an adjunctive treatment for infectious diseases. This study investigates the immunomodulatory effects of ImiP in B. abortus 544 infections in murine macrophages and BALB/c mice. In vitro, RAW 264.7 cells exposed to ImiP exhibited reduced B. abortus replication, decreased nitrite levels, and enhanced bactericidal effects. In vivo, ImiP treatment significantly decreased bacterial loads in the spleen (10 mg/kg, **p < 0.01; 20 mg/kg, *p < 0.05) and liver (10 mg/kg, **p < 0.01; 20 mg/kg, ***p < 0.001), compared to untreated controls. Histopathological analysis revealed minimal liver microgranuloma formation and periportal inflammation in ImiP-treated mice. Moreover, flow cytometry showed decreased CD4+ and CD8+ T cell expression, while serum cytokine profiling indicated a Th1-driven immune response, characterized by elevated levels of IL-12 and decreased IL-10. These findings suggest that ImiP possesses both immunomodulatory and antibacterial effects, highlighting its potential as an adjunctive therapy for brucellosis.
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spelling doaj-art-e7867bb7d47b407e94594891ea9352382025-08-20T03:20:10ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692025-06-011210.3389/fvets.2025.15981061598106Imipramine-induced immunomodulation and intracellular growth inhibition during Brucella abortus 544 infection in RAW 264.7 cells and BALB/c miceChed Nicole Turbela Aguilar0Tran Xuan Ngoc Huy1Trang Thi Nguyen2Said Abdi Salad3Seong Eun Cho4Il-Hwa Hong5Wongi Min6Hu Jang Lee7Suk Kim8Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of KoreaInstitute of Applied Sciences, HUTECH University, Ho Chi Minh City, VietnamInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of KoreaInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of KoreaInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of KoreaInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of KoreaInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of KoreaInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of KoreaInstitute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of KoreaBrucellosis is a significant zoonotic infection with increasing global prevalence. Traditional treatments rely on antibiotic combinations, but challenges such as drug resistance and relapse necessitate the exploration of alternative therapeutic options. Imipramine hydrochloride (ImiP) has shown potential as an adjunctive treatment for infectious diseases. This study investigates the immunomodulatory effects of ImiP in B. abortus 544 infections in murine macrophages and BALB/c mice. In vitro, RAW 264.7 cells exposed to ImiP exhibited reduced B. abortus replication, decreased nitrite levels, and enhanced bactericidal effects. In vivo, ImiP treatment significantly decreased bacterial loads in the spleen (10 mg/kg, **p < 0.01; 20 mg/kg, *p < 0.05) and liver (10 mg/kg, **p < 0.01; 20 mg/kg, ***p < 0.001), compared to untreated controls. Histopathological analysis revealed minimal liver microgranuloma formation and periportal inflammation in ImiP-treated mice. Moreover, flow cytometry showed decreased CD4+ and CD8+ T cell expression, while serum cytokine profiling indicated a Th1-driven immune response, characterized by elevated levels of IL-12 and decreased IL-10. These findings suggest that ImiP possesses both immunomodulatory and antibacterial effects, highlighting its potential as an adjunctive therapy for brucellosis.https://www.frontiersin.org/articles/10.3389/fvets.2025.1598106/fullBrucella abortusimipramine hydrochlorideBALB/c mouseRAW 264.7 cellsimmunomodulation
spellingShingle Ched Nicole Turbela Aguilar
Tran Xuan Ngoc Huy
Trang Thi Nguyen
Said Abdi Salad
Seong Eun Cho
Il-Hwa Hong
Wongi Min
Hu Jang Lee
Suk Kim
Imipramine-induced immunomodulation and intracellular growth inhibition during Brucella abortus 544 infection in RAW 264.7 cells and BALB/c mice
Frontiers in Veterinary Science
Brucella abortus
imipramine hydrochloride
BALB/c mouse
RAW 264.7 cells
immunomodulation
title Imipramine-induced immunomodulation and intracellular growth inhibition during Brucella abortus 544 infection in RAW 264.7 cells and BALB/c mice
title_full Imipramine-induced immunomodulation and intracellular growth inhibition during Brucella abortus 544 infection in RAW 264.7 cells and BALB/c mice
title_fullStr Imipramine-induced immunomodulation and intracellular growth inhibition during Brucella abortus 544 infection in RAW 264.7 cells and BALB/c mice
title_full_unstemmed Imipramine-induced immunomodulation and intracellular growth inhibition during Brucella abortus 544 infection in RAW 264.7 cells and BALB/c mice
title_short Imipramine-induced immunomodulation and intracellular growth inhibition during Brucella abortus 544 infection in RAW 264.7 cells and BALB/c mice
title_sort imipramine induced immunomodulation and intracellular growth inhibition during brucella abortus 544 infection in raw 264 7 cells and balb c mice
topic Brucella abortus
imipramine hydrochloride
BALB/c mouse
RAW 264.7 cells
immunomodulation
url https://www.frontiersin.org/articles/10.3389/fvets.2025.1598106/full
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