Stark James M, Stark Marilyn A, Colasurdo Giuseppe N, LeVine Ann Marie
Department of Pediatrics, University of Texas Health Science Center at Houston, 77030, USA.
J Med Virol. 2006 Jun;78(6):829-38. doi: 10.1002/jmv.20631.
Virus respiratory infections often precede bacterial pneumonia in healthy individuals. In order to determine the potential role of respiratory syncytial virus (RSV) in bacterial secondary infections, a mouse sequential pulmonary infection model was developed. Mice were exposed to RSV then challenged with Streptococcus pneumoniae (StPn). Exposure of BALB/c mice to 10(6)-10(7) plaque forming units (pfu) of virus of RSV significantly decreased StPn clearance 1-7 days following RSV exposure. This finding was not restricted to StPn alone: exposure to RSV followed by Staphylococcus aureus (SA) or Pseudomonas aeruginosa(PA) resulted in similar decreases in bacterial clearance. Both bronchoalveolar lavage (BAL) cell counts and pulmonary histopathology demonstrated that RSV-StPn exposed mice had increased lung cellular inflammation compared to mice receiving StPn or RSV alone. The effect of RSV infection on bacterial clearance was dependent on the mouse genetic background: C57BL/6J mice (relatively resistant to RSV infection) demonstrated a modest change in StPn clearance following RSV exposure, whereas FVBN/J mice (similar to the BALB/cJ mice in RSV susceptibility) demonstrated a similar degree of RSV-associated decrease in StPn clearance 7 days following RSV exposure. Neutrophils from the RSV-StPn sequentially exposed BALB/cJ mice were functionally altered-produced greater levels of peroxide production but less myeloperoxidase (MPO) compared to mice receiving StPn alone. These data demonstrate that RSV infection decreases bacterial clearance, potentially predisposing to secondary bacterial pneumonia despite increased lung cellular inflammation, and suggest that functional changes occur in the recruited neutrophils that may contribute to the decreased bacterial clearance.
在健康个体中，病毒呼吸道感染常常先于细菌性肺炎出现。为了确定呼吸道合胞病毒（RSV）在细菌性继发感染中的潜在作用，建立了一种小鼠序贯肺部感染模型。将小鼠暴露于RSV，然后用肺炎链球菌（StPn）进行攻击。BALB/c小鼠暴露于10⁶ - 10⁷个RSV病毒蚀斑形成单位（pfu）后，在RSV暴露后1 - 7天，StPn清除率显著降低。这一发现并不局限于单独的StPn：暴露于RSV后再感染金黄色葡萄球菌（SA）或铜绿假单胞菌（PA）也导致细菌清除率出现类似下降。支气管肺泡灌洗（BAL）细胞计数和肺部组织病理学均表明，与单独接受StPn或RSV的小鼠相比，暴露于RSV - StPn的小鼠肺部细胞炎症增加。RSV感染对细菌清除的影响取决于小鼠的遗传背景：C57BL/6J小鼠（对RSV感染相对有抵抗力）在暴露于RSV后，StPn清除率有适度变化，而FVBN/J小鼠（在RSV易感性方面与BALB/cJ小鼠相似）在RSV暴露7天后，StPn清除率出现与RSV相关的类似程度下降。与单独接受StPn的小鼠相比，序贯暴露于RSV - StPn的BALB/cJ小鼠的中性粒细胞功能发生改变——产生更高水平的过氧化物，但髓过氧化物酶（MPO）水平较低。这些数据表明，RSV感染会降低细菌清除率，尽管肺部细胞炎症增加，但仍可能易患继发性细菌性肺炎，并且提示募集的中性粒细胞发生功能变化，这可能导致细菌清除率下降。
