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Published on: February 23, 2014
Cytomegalovirus reactivation enhances the virulence of Staphylococcus aureus pneumonia in a mouse model
Objectives:
Cytomegalovirus (CMV) reactivation in intensive care unit patients may increase mortality and favour bacterial pneumonia. We developed a murine model to compare the severity of staphylococcal pneumonia after CMV reactivation and in CMV-negative mice.
Methods:
Balb/c mice were primo-infected with murine cytomegalovirus (MCMV n=90) or received saline (control n=90). After latency, all mice underwent caecal ligation and puncture to trigger MCMV reactivation in MCMV primary-infected mice. Surviving animals received an intra-nasal inoculation with methicillin-susceptible Staphylococcus aureus (MSSA) to induce pneumonia. Mortality, lung bacterial count, histology and interferon-alpha and gamma serum levels were compared in MCMV reactivated and control mice 2, 5 and 15 days after pneumonia.
Results:
After MSSA pneumonia, MCMV mice showed a trend towards a higher mortality (9.4% versus 0%; p 0.09) and a higher weight loss (2.2 (0.6-4.1 g) versus 0.7 (-0.3 to 1.3 g); p 0.005). The lung bacterial count was higher in MCMV mice 2 days (5×103 (103 to 3×105) versus 102 (0 to 4×102) CFU/lung; p 0.007) and 5 days (2.5×104 (1.6×104 to 6.5×105) versus 15 (10-40) CFU/lung; p 0.005) after MSSA pneumonia. 8/40 (20%) MCMV mice developed lung abscesses compared to 0% in control (p 0.011). Interferon-alpha serum levels 2 days after staphylococcal pneumonia were higher in MCMV mice.
Conclusions:
MCMV reactivation decreased lung bacterial clearance and favoured the development of staphylococcal abscessing pneumonia. CMV reactivation may be responsible for a higher susceptibility to bacterial sepsis.
Insights
Cytomegalovirus (CMV) reactivation in mice worsened Staphylococcus aureus pneumonia, increasing mortality and lung bacterial load. This suggests CMV reactivation heightens susceptibility to bacterial sepsis.
Area of Science:
- Infectious Disease
- Immunology
- Pulmonology
Background:
- Cytomegalovirus (CMV) reactivation is linked to increased mortality in intensive care unit patients.
- CMV reactivation may predispose patients to secondary bacterial pneumonia.
Purpose of the Study:
- To establish a murine model for investigating the impact of CMV reactivation on bacterial pneumonia severity.
- To compare staphylococcal pneumonia outcomes in mice with and without CMV reactivation.
Main Methods:
- Balb/c mice were infected with murine cytomegalovirus (MCMV) or saline, followed by a caecal ligation and puncture to induce MCMV reactivation.
- Pneumonia was induced via intra-nasal inoculation with methicillin-susceptible Staphylococcus aureus (MSSA).
- Mortality, lung bacterial counts, histology, and serum cytokine levels were assessed post-pneumonia.
Main Results:
- Mice with MCMV reactivation exhibited a trend towards higher mortality and significant weight loss after MSSA pneumonia.
- Lung bacterial counts were significantly elevated in MCMV-reactivated mice at 2 and 5 days post-pneumonia.
- A higher incidence of lung abscesses was observed in MCMV-reactivated mice, alongside elevated interferon-alpha levels.
Conclusions:
- Murine cytomegalovirus reactivation impairs bacterial clearance and promotes the development of severe, abscessing staphylococcal pneumonia.
- CMV reactivation may increase susceptibility to severe bacterial infections, including sepsis.
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