Related Experiment Video
Updated: Aug 15, 2026
A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
The pathogenesis of Staphylococcus aureus infection in the diabetic NOD mouse
1Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Abstract:
Although Staphylococcus aureus is a major pathogen implicated in diabetic foot infections, little is known about the pathogenesis of this disease. A model of S. aureus infection in the hindpaw of nonobese diabetic (NOD) mice was developed. The experimental infection was exacerbated in diabetic mice (blood glucose levels > or =19 mmol/l) compared with nondiabetic mice, and the diabetic animals were unable to clear the infection over a 10-day period. Insulin-mediated control of glycemia in diabetic mice resulted in enhanced clearance of S. aureus from the infected tissue. Diabetic mice showed reduced tissue inflammation in response to bacterial inoculation compared with nondiabetic NOD animals, and this was consistent with the novel finding of significantly decreased tissue levels of the chemokines KC and MIP-2 in diabetic mice. Blood from nondiabetic and diabetic NOD mice killed S. aureus in vitro, whereas the bacteria multiplied in blood from diabetic mice with severe hyperglycemia. The impaired killing of S. aureus by diabetic mice was correlated with a diminished leukocytic respiratory burst in response to S. aureus in blood from diabetic animals. This animal model of hindpaw infection may be useful for the analysis of host defects in innate immunity that contribute to recalcitrant diabetic foot infections.
Insights
Diabetic mice exhibit impaired Staphylococcus aureus infection clearance due to hyperglycemia, affecting innate immunity. Controlling blood glucose levels in diabetic mice enhances bacterial clearance and reduces infection severity.
Area of Science:
- Microbiology
- Immunology
- Diabetology
Background:
- Staphylococcus aureus is a significant pathogen in diabetic foot infections.
- The pathogenesis of these infections remains poorly understood.
- Diabetic foot infections are often difficult to treat and slow to heal.
Purpose of the Study:
- To develop and characterize a mouse model for studying Staphylococcus aureus hindpaw infections in diabetic individuals.
- To investigate the impact of hyperglycemia on the host's immune response and bacterial clearance.
- To identify specific immune defects contributing to recalcitrant diabetic foot infections.
Main Methods:
- Development of a hindpaw infection model in nonobese diabetic (NOD) mice.
- Comparison of S. aureus infection outcomes between diabetic and nondiabetic NOD mice.
- Assessment of bacterial clearance, tissue inflammation, chemokine levels (KC and MIP-2), and blood's ability to kill S. aureus.
- Evaluation of leukocytic respiratory burst in response to S. aureus.
Main Results:
- Diabetic mice showed exacerbated S. aureus infection and impaired bacterial clearance compared to nondiabetic mice.
- Insulin-mediated glycemic control improved S. aureus clearance in diabetic mice.
- Diabetic mice exhibited reduced tissue inflammation and lower levels of chemokines KC and MIP-2.
- Hyperglycemia in diabetic mice correlated with impaired bacterial killing in blood and diminished leukocytic respiratory burst.
Conclusions:
- Hyperglycemia significantly exacerbates Staphylococcus aureus infections in a diabetic mouse model.
- Impaired innate immune responses, including reduced chemokine production and leukocytic dysfunction, contribute to infection severity.
- This model provides a valuable tool for studying host immune defects in diabetic foot infections and evaluating potential therapeutic strategies.
