Related Experiment Video
Updated: May 3, 2026
Intravital Imaging of Neutrophil Priming Using IL-1β Promoter-driven DsRed Reporter Mice
Published on: June 22, 2016
IFN-γ-deficient mice develop IL-1-dependent cutaneous and musculoskeletal inflammation during experimental
Jerod A Skyberg1, Theresa Thornburg, Irina Kochetkova
1Department of Immunology and Infectious Diseases, Montana State University, Bozeman, Montana, USA.
Abstract:
Human brucellosis exhibits diverse pathological manifestations that can affect almost any organ. In particular, osteoarticular complications are the most common focal manifestation of brucellosis and occur in 40-80% of patients. In immunocompetent mice, Brucella replication is generally restricted to the spleen, liver, and to a lesser extent, LNs, thereby limiting their use for study of focal inflammation often found in brucellosis. Here, we report that nasal, oral, or peritoneal infection of IFN-γ(-/-) mice with WT Brucella melitensis or Brucella abortus results in joint and periarticular tissue inflammation. Histological analysis of the affected joints revealed inflammatory infiltrates and debris within the joint space colocalizing with Brucella antigen. Osteoarthritis, necrosis, periarticular soft tissue inflammation, and substantial brucellae burdens were observed. Oral rifampicin was effective in clearing infection and halting further progression of focal inflammation from infected IFN-γ(-/-) mice, although some symptoms and swelling remained. Elevated IL-1 β, but not TNF-α, IL-6, or IL-17, was detected in joint homogenates from infected IFN-γ(-/-) mice. Whereas more susceptible to systemic infection, IL-1R(-/-) mice depleted of IFN-γ were more resistant to focal inflammation than WT mice similarly depleted of IFN-γ. Collectively, these results show IFN-γ(-/-) mice represent a potential model for study of focal inflammation attributed to Brucella infection and will allow evaluation of intervention strategies targeting IL-1, IL-1R, or other inflammatory mediators, with the potential to complement antibiotic-based therapies.
Insights
Interferon-gamma knockout mice develop joint inflammation after Brucella infection, offering a new model to study this focal manifestation of brucellosis and test anti-inflammatory treatments.
Area of Science:
- Immunology
- Microbiology
- Pathology
Background:
- Human brucellosis presents diverse pathological effects, with osteoarticular complications being the most frequent focal manifestation.
- Brucella infection in immunocompetent mice is typically limited to spleen, liver, and lymph nodes, hindering the study of focal inflammation.
Purpose of the Study:
- To establish a mouse model for studying focal inflammation in brucellosis, specifically targeting joint and periarticular tissues.
- To investigate the role of interferon-gamma (IFN-γ) in Brucella-induced focal inflammation and evaluate therapeutic interventions.
Main Methods:
- Infection of IFN-γ knockout (IFN-γ(-/-)) mice via nasal, oral, or peritoneal routes with Brucella melitensis or Brucella abortus.
- Histological analysis of affected joints to identify inflammatory infiltrates, Brucella antigen, and pathological changes like osteoarthritis and necrosis.
- Assessment of inflammatory mediators (IL-1β, TNF-α, IL-6, IL-17) in joint homogenates and evaluation of oral rifampicin treatment efficacy.
Main Results:
- IFN-γ(-/-) mice infected with Brucella developed significant joint and periarticular inflammation, characterized by inflammatory infiltrates, osteoarthritis, necrosis, and high bacterial loads.
- Oral rifampicin treatment reduced infection and inflammation progression, though some symptoms persisted.
- Elevated levels of IL-1β were detected in joint homogenates, while TNF-α, IL-6, and IL-17 remained unchanged.
- Mice lacking both IL-1 receptor (IL-1R(-/-)) and IFN-γ showed resistance to focal inflammation compared to IFN-γ(-/-) wild-type mice.
Conclusions:
- IFN-γ(-/-) mice serve as a valuable model for investigating Brucella-induced focal inflammation, particularly osteoarticular complications.
- This model facilitates the evaluation of therapeutic strategies targeting IL-1, IL-1R, and other inflammatory mediators as adjuncts to antibiotic therapy for brucellosis.
