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Updated: Sep 11, 2025
Chronic Salmonella Infected Mouse Model
Published on: May 31, 2010
Effect of TRIM67 knockout on inflammation and macrophage survival in Salmonella Typhimurium-infected mice
Shuxi Chen1, Xinyue Zhang2, Zongliang Xiong2
1Laboratory of Experimental Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China.
Abstract:
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a pathogenic bacterium that causes acute gastroenteritis. Macrophages play a crucial role in modulating inflammatory responses and eliminating S. Typhimurium infections. In this study, we identified TRIM67, a tripartite motif protein, as a key mediator of macrophage immunity against S. Typhimurium infection. Using S. Typhimurium mouse models, we evaluated the impact of TRIM67 deficiency on liver and spleen inflammation under both normal physiological conditions and S. Typhimurium infection. Mechanistic insights into TRIM67-mediated inflammatory effects were investigated through immunohistochemistry and Western blotting. For in vitro experiments, primary peritoneal macrophages were isolated from Wild-Type(WT) and TRIM67-knockout(KO) mice, and generated TRIM67-overexpressing RAW 264.7 macrophage cell lines. We assessed bacterial load, survival rates, and macrophage-mediated immune responses following S. Typhimurium infection. Our results demonstrated that KO mice exhibited heightened susceptibility to S. Typhimurium infection compared to WT mice. TRIM67 knockout suppressed inflammation in the liver and spleen, impaired monocyte recruitment to infection sites, and reduced macrophage numbers, ultimately leading to increased mortality. Furthermore, TRIM67 knockout inhibited the activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways, thereby attenuating macrophage immunity and the production of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. This study unveils a novel role for TRIM67 in protecting mice against S. Typhimurium infection by regulating inflammation and macrophage survival.
Insights
The study found that TRIM67 protein is crucial for macrophage immunity against Salmonella Typhimurium infection. TRIM67 deficiency increases susceptibility to infection and mortality by impairing immune responses.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Salmonella Typhimurium causes gastroenteritis, with macrophages critical for host defense.
- The role of tripartite motif protein 67 (TRIM67) in macrophage immunity against bacterial pathogens is largely unknown.
Purpose of the Study:
- To investigate the role of TRIM67 in macrophage-mediated immunity against Salmonella Typhimurium infection.
- To elucidate the mechanisms underlying TRIM67's function in regulating inflammatory responses and host defense.
Main Methods:
- Utilized Salmonella Typhimurium mouse models and primary peritoneal macrophages from wild-type and TRIM67-knockout mice.
- Employed immunohistochemistry, Western blotting, and macrophage cell lines to assess bacterial load, survival, inflammation, and signaling pathways.
- Evaluated TRIM67's impact on liver and spleen inflammation, monocyte recruitment, and cytokine production (TNF-α, IL-1β, IL-6).
Main Results:
- TRIM67-knockout mice showed increased susceptibility and mortality to S. Typhimurium infection.
- TRIM67 deficiency suppressed liver and spleen inflammation, impaired monocyte recruitment, and reduced macrophage numbers.
- Knockout of TRIM67 inhibited MAPK and NF-κB signaling pathways, reducing pro-inflammatory cytokine production.
Conclusions:
- TRIM67 plays a vital protective role against Salmonella Typhimurium infection.
- TRIM67 regulates inflammation and macrophage survival, crucial for effective host defense.
- TRIM67 is a novel mediator of macrophage immunity against S. Typhimurium.
