Cytomegalovirus reactivation enhances the virulence of Staphylococcus aureus pneumonia in a mouse model

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• 作者：S. Hraiech¹ ; ² ; ^{sami.hraiech@ap-hm.fr} ; J. Bordes² ; ³ ; J.L. Mè ; ge² ; X. de Lamballerie⁴ ; ⁵ ; R. Charrel⁴ ; ⁵ ; Y. Bechah² ; B. Pastorino⁴ ; ⁵ ; C. Guervilly¹ ; J.M. Forel¹ ; M. Adda¹ ; J.M. Rolain² ; H. Lepidi² ; D. Raoult² ; S. Lehingue¹ ; L. Papazian¹ ; ²
• 关键词：Cytomegalovirus reactivation ; Intensive care unit ; Lung abscesses ; Murine model ; Pneumonia ; Staphylococcus aureus
• 刊名：Clinical Microbiology and Infection
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：23
• 期：1
• 页码：38-45
• 全文大小：950 K
• 卷排序：23

文摘

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.MethodsBalb/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.ResultsAfter 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.ConclusionsMCMV 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.