IL-10 is an important mediator of the enhanced susceptibility to pneumococcal pneumonia after influenza infection
IL-10 is an important mediator of the enhanced susceptibility to pneumococcal pneumonia after influenza infection
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DOI：
10.4049/jimmunol.172.12.7603
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发表时间：
2004-06-15
影响因子：
4.4
通讯作者：
van der Poll, T
中科院分区：
文献类型：
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作者：
van der Sluijs, KF;van Elden, LJR;van der Poll, T
继发性肺炎球菌肺炎是流感感染期间和感染后不久的严重并发症。我们建立了一个小鼠模型来研究流感后肺炎球菌肺炎，并评估了IL-10在流感感染恢复后宿主防御肺炎链球菌的作用。在第0天用10个中值组织培养感染剂量的甲型流感（A/PR/8/34）或PBS（对照）鼻内接种C57 BL/6小鼠。到第14天，小鼠已经恢复了正常体重，并且通过实时定量PCR测定，已经从肺部清除了流感病毒。在病毒感染后第14天，小鼠接受10（4）CFU的S.肺炎（血清型3）鼻内给药。从流感感染中恢复的小鼠对随后的肺炎球菌肺炎高度敏感，如细菌感染后第3天100%的致死率所反映的，而对照小鼠在肺炎球菌感染后第3天显示17%的致死率，第6天显示83%的致死率。此外，在感染S.在流感恢复小鼠中观察到肺炎，特别是肺部IL-10水平比对照小鼠高50倍。与IgG 1对照小鼠相比，在细菌接种前1小时用抗IL-10 mAb治疗导致继发性细菌性肺炎期间细菌生长减少和致死率显著降低。总之，轻度自限性甲型流感感染使正常免疫活性小鼠对肺炎球菌肺炎高度敏感。这种对继发性细菌性肺炎的易感性增加至少部分是由肺中过量的IL-10产生和中性粒细胞功能降低引起的。
Secondary pneumococcal pneumonia is a serious complication during and shortly after influenza infection. We established a mouse model to study postinfluenza pneumococcal pneumonia and evaluated the role of IL-10 in host defense against Streptococcus pneunioniae after recovery from influenza infection. C57BL/6 mice were intranasally inoculated with 10 median tissue culture infective doses of influenza A (A/PR/8/34) or PBS (control) on day 0. By day 14 mice had regained their normal body weight and had cleared influenza virus from the lungs, as determined by real-time quantitative PCR. On day 14 after viral infection, mice received 10(4) CFU of S. pneunioniae (serotype 3) intranasally. Mice recovered from influenza infection were highly susceptible to subsequent pneumococcal pneumonia, as reflected by a 100% lethality on day 3 after bacterial infection, whereas control mice showed 17% lethality on day 3 and 83% lethality on day 6 after pneumococcal infection. Furthermore, 1000-fold higher bacterial counts at 48 h after infection with S. pneumoniae and, particularly, 50-fold higher pulmonary levels of IL-10 were observed in influenza-recovered mice than in control mice. Treatment with an anti-IL-10 mAb 1 h before bacterial inoculation resulted in reduced bacterial outgrowth and markedly reduced lethality during secondary bacterial pneumonia compared with those in IgG1 control mice. In conclusion, mild self-limiting influenza A infection renders normal immunocompetent mice highly susceptible to pneumococcal pneumonia. This increased susceptibility to secondary bacterial pneumonia is at least in part caused by excessive IL-10 production and reduced neutrophil function in the lungs.