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Role of macrophages in experimental group B streptococcal arthritis
Manuela Puliti1, Christina von Hunolstein, Francesco Bistoni
1Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy.
Abstract:
Septic arthritis is a clinical manifestation of group B Streptococcus (GBS) infection in both neonates and adults. Because macrophages are known to participate in tissue injury, the role of this cell population in GBS-induced arthritis was investigated. Mice were rendered monocytopenic by administration of etoposide, a drug that selectively depletes the monocyte/macrophage population and then injected with GBS (1 x 10(7) colony-forming units per mouse). Appearance of arthritis, mortality, GBS growth in the organs, and local and systemic cytokine production were examined. Etoposide-treated mice had a significantly less severe arthritis than control animals. Histopathological analysis of the joints confirmed clinical observations. Decreased joint levels of the proinflammatory cytokines interleukin 1 (IL-1) beta and IL-6 accompanied the less severe development of arthritis in monocytopenic mice. In contrast, mortality was increased in the etoposide-treated mice compared with controls. Monocytopenic mice exhibited elevated bacterial load in the blood and kidneys at all time points examined. These results indicate that lack of macrophages leads to less severe joint lesions, but also results in impaired clearance of bacteria, and consequent enhancement of mortality rates.
Insights
Macrophages worsen septic arthritis but aid bacterial clearance. Depleting macrophages in mice reduced joint inflammation from group B Streptococcus (GBS) infection but increased mortality due to higher bacterial loads.
Area of Science:
- Immunology
- Microbiology
- Rheumatology
Background:
- Septic arthritis is a joint inflammation caused by bacterial infection.
- Group B Streptococcus (GBS) is a significant pathogen causing septic arthritis in neonates and adults.
- Macrophages are immune cells implicated in both host defense and tissue damage during infection.
Purpose of the Study:
- To investigate the role of macrophages in the pathogenesis of GBS-induced septic arthritis.
- To determine the impact of macrophage depletion on arthritis severity, bacterial burden, and host survival.
Main Methods:
- Mice were treated with etoposide to deplete circulating monocytes and macrophages.
- Etoposide-treated and control mice were infected with GBS.
- Arthritis development, mortality, bacterial growth in organs, and cytokine levels were assessed.
Main Results:
- Monocytopenic mice exhibited significantly less severe arthritis and reduced joint levels of IL-1β and IL-6.
- Despite reduced joint inflammation, monocytopenic mice showed increased mortality.
- Bacterial load was significantly higher in the blood and kidneys of etoposide-treated mice.
Conclusions:
- Macrophages contribute to the inflammatory joint pathology in GBS septic arthritis.
- However, macrophages are crucial for controlling GBS dissemination and ensuring host survival.
- Targeting macrophages in GBS infection requires careful consideration of the trade-off between inflammation and bacterial clearance.