Department of Paediatrics, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China.
BMC Infect Dis. 2011 Jul 20;11:201. doi: 10.1186/1471-2334-11-201.
Influenza virus is a major cause of respiratory disease worldwide and Streptococcus pneumoniae infection associated with influenza often leads to severe complications. Dendritic cells are key antigen presenting cells but its role in such co-infection is unclear.
In this study, human monocyte derived-dentritic cells were either concurrently or successively challenged with the combination of live influenza virus and heat killed pneumococcus to mimic the viral pneumococcal infection. Dendritic cell viability, phenotypic maturation and cytokine production were then examined.
The challenge of influenza virus and pneumococcus altered dendritic cell functions dependent on the time interval between the successive challenge of influenza virus and pneumococcus, as well as the doses of pneumococcus. When dendritic cells were exposed to pneumococcus at 6 hr, but not 0 hr nor 24 hr after influenza virus infection, both virus and pneumococcus treated dendritic cells had greater cell apoptosis and expressed higher CD83 and CD86 than dendritic cells infected with influenza virus alone. Dendritic cells produced pro-inflammatory cytokines: TNF-α, IL-12 and IFN-γ synergistically to the successive viral and pneumococcal challenge. Whereas prior influenza virus infection suppressed the IL-10 response independent of the timing of the subsequent pneumococcal stimulation.
Our results demonstrated that successive challenge of dendritic cells with influenza virus and pneumococcus resulted in synergistic up-regulation of pro-inflammatory cytokines with simultaneous down-regulation of anti-inflammatory cytokine, which may explain the immuno-pathogenesis of this important co-infection.
流感病毒是全球范围内导致呼吸道疾病的主要原因，流感病毒感染相关的肺炎链球菌感染常导致严重并发症。树突状细胞是主要的抗原呈递细胞，但在这种合并感染中的作用尚不清楚。
在这项研究中，人单核细胞来源的树突状细胞同时或先后受到活流感病毒和热灭活肺炎链球菌的联合挑战，以模拟病毒-肺炎链球菌感染。然后检查树突状细胞的活力、表型成熟和细胞因子产生。
流感病毒和肺炎链球菌的挑战改变了树突状细胞的功能，这取决于流感病毒和肺炎链球菌相继挑战之间的时间间隔以及肺炎链球菌的剂量。当树突状细胞在流感病毒感染后 6 小时而不是 0 小时或 24 小时暴露于肺炎链球菌时，与单独感染流感病毒的树突状细胞相比，病毒和肺炎链球菌处理的树突状细胞凋亡更多，并且表达更高水平的 CD83 和 CD86。树突状细胞产生促炎细胞因子：TNF-α、IL-12 和 IFN-γ协同作用于连续的病毒和肺炎链球菌挑战。而先前的流感病毒感染抑制了 IL-10 反应，而与随后肺炎链球菌刺激的时间无关。
我们的结果表明，树突状细胞连续受到流感病毒和肺炎链球菌的挑战会协同上调促炎细胞因子，同时下调抗炎细胞因子，这可能解释了这种重要合并感染的免疫发病机制。
