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.