Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
J Infect Dis. 2014 Mar;209(6):865-75. doi: 10.1093/infdis/jit527. Epub 2013 Sep 26.
Influenza A represents a significant cause of morbidity and mortality worldwide. Bacterial complications of influenza A confer the greatest risk to patients. TH17 pathway inhibition has been implicated as a mechanism by which influenza A alters bacterial host defense. Here we show that preceding influenza causes persistent Staphylococcus aureus infection and suppression of TH17 pathway activation in mice. Influenza does not inhibit S. aureus binding and uptake by phagocytic cells but instead attenuates S. aureus induced TH17 related antimicrobial peptides necessary for bacterial clearance in the lung. Importantly, exogenous lipocalin 2 rescued viral exacerbation of S. aureus infection and decreased free iron levels in the bronchoalveolar lavage from mice coinfected with S. aureus and influenza. These findings indicate a novel mechanism by which influenza A inhibits TH17 immunity and increases susceptibility to secondary bacterial pneumonia. Identification of new mechanisms in the pathogenesis of bacterial pneumonia could lead to future therapeutic targets.
甲型流感病毒是全球范围内发病率和死亡率的重要原因。甲型流感的细菌并发症给患者带来最大的风险。TH17 途径抑制被认为是甲型流感改变细菌宿主防御的一种机制。在这里，我们表明，流感前会导致金黄色葡萄球菌持续感染，并抑制小鼠中 TH17 途径的激活。流感并不会抑制吞噬细胞对金黄色葡萄球菌的结合和摄取，但会减弱金黄色葡萄球菌诱导的 TH17 相关抗菌肽，这些抗菌肽是肺部清除细菌所必需的。重要的是，外源性脂联素 2 挽救了病毒加重金黄色葡萄球菌感染，并降低了金黄色葡萄球菌和流感病毒共感染小鼠支气管肺泡灌洗液中的游离铁水平。这些发现表明了甲型流感病毒抑制 TH17 免疫并增加继发性细菌性肺炎易感性的一种新机制。鉴定细菌性肺炎发病机制中的新机制可能为未来的治疗靶点提供线索。
