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Updated: Jul 3, 2026
A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection
Published on: February 28, 2019
Neutrophil depletion causes a fatal defect in murine pulmonary Staphylococcus aureus clearance
Charles M Robertson1, Erin E Perrone, Kevin W McConnell
1Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Background:
Staphylococcus aureus is the most common cause of healthcare-associated pneumonia. Despite the significant morbidity and mortality associated with the disease, animal models of S. aureus pneumonia are rare.
Materials And Methods:
We examined the pathogenicity of four different strains of S. aureus (both methicillin-sensitive and -resistant as well as Panton-Valentine leukocidin-positive and -negative) in four strains of immunocompetent inbred and outbred mice (FVB/N, C57Bl/6, BALB/c, ND4; n = 148). The immunological basis for the development of murine S. aureus pneumonia was then determined by selectively depleting neutrophils, lymphocytes, or pulmonary macrophages prior to the onset of infection. An additional cohort of animals was rendered immunosuppressed by induction of abdominal sepsis via cecal ligation and puncture 2, 4, or 7 d prior to the onset of pneumonia.
Results:
Nearly all immunocompetent mice survived, regardless of which strain of S. aureus was used or which strain of mouse was infected. Among animals with immune depletion or prior immunosuppression, survival was decreased only following neutrophil depletion (26% versus 90% alive at 7 d, P < 0.0001). Compared to immunocompetent animals, neutrophil-depleted mice with S. aureus pneumonia had delayed pulmonary bacterial clearance at 16 and 40 h but had no difference in levels of bacteremia. Neutrophil-depleted mice also had elevated levels of pulmonary monocyte chemotactic protein-1 (822 pg/mL versus 150 pg/mL, P < 0.05). In contrast, pulmonary histological appearance was similar in both groups as was dry/wet lung weight.
Conclusions:
These results suggest that neutrophils play a critical role in the host response to S. aureus pneumonia, and the survival differences observed in neutrophil-depleted mice are associated with alterations in bacterial clearance and pulmonary cytokine response.
Insights
Neutrophils are critical for fighting Staphylococcus aureus pneumonia. Depleting neutrophils significantly reduced survival in mice, impacting bacterial clearance and lung inflammation.
Area of Science:
- Infectious Diseases
- Immunology
- Pulmonary Medicine
Background:
- Staphylococcus aureus is a leading cause of healthcare-associated pneumonia.
- Animal models for S. aureus pneumonia are scarce, limiting research.
- Understanding host response is crucial for effective treatment.
Purpose of the Study:
- To investigate the pathogenicity of S. aureus strains in mice.
- To determine the immunological basis of S. aureus pneumonia.
- To evaluate the role of neutrophils, lymphocytes, and macrophages in host defense.
Main Methods:
- Tested four S. aureus strains in four mouse strains (n=148).
- Assessed immune cell depletion (neutrophils, lymphocytes, macrophages).
- Induced immunosuppression via cecal ligation and puncture.
Main Results:
- Immunocompetent mice showed high survival rates.
- Neutrophil depletion significantly decreased survival (26% vs 90% at 7 days).
- Neutrophil-depleted mice had delayed bacterial clearance and elevated pulmonary monocyte chemotactic protein-1.
Conclusions:
- Neutrophils are essential for host defense against S. aureus pneumonia.
- Neutrophil depletion impairs bacterial clearance and alters pulmonary cytokine response.
- Findings highlight neutrophils as a key therapeutic target.
