Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Victoria, Australia.
Infect Immun. 2013 Mar;81(3):645-52. doi: 10.1128/IAI.01278-12. Epub 2013 Jan 14.
Influenza A virus (IAV) predisposes individuals to secondary infections with the bacterium Streptococcus pneumoniae (the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis, or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV-induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes such as OM. Here, we used an infant mouse model, human middle ear epithelial cells, and a series of reverse-engineered influenza viruses to investigate how IAV promotes bacterial OM. Our data suggest that the influenza virus HA facilitates disease by inducing a proinflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings suggest that it is the inflammatory response to IAV infection that mediates pneumococcal replication. This study thus provides the first evidence that inflammation drives pneumococcal replication in the middle ear cavity, which may have important implications for the treatment of pneumococcal OM.
甲型流感病毒（IAV）使个体易发生细菌肺炎链球菌（肺炎球菌）的继发感染。感染可能表现为肺炎、败血症、脑膜炎或中耳炎（OM）。目前仍存在争议的是，继发性肺炎球菌病是由于诱导异常免疫反应还是 IAV 诱导的免疫抑制引起的。此外，由于大多数研究都是在肺炎球菌性肺炎的背景下进行的，因此尚不清楚这些发现可以在多大程度上推广到其他肺炎球菌病表型，如 OM。在这里，我们使用婴儿小鼠模型、人中耳上皮细胞和一系列反向工程流感病毒来研究 IAV 如何促进细菌 OM。我们的数据表明，流感病毒 HA 通过以依赖复制的方式在中耳腔中诱导促炎反应来促进疾病。重要的是，我们的研究结果表明，介导肺炎球菌复制的是对 IAV 感染的炎症反应。因此，这项研究首次提供了证据表明炎症驱动中耳腔内肺炎球菌的复制，这可能对肺炎球菌性 OM 的治疗具有重要意义。
