Type 1 interferon gene transfer enhances host defense against pulmonary Streptococcus pneumoniae infection via activating innate leukocytes.
Type 1 interferon gene transfer enhances host defense against pulmonary Streptococcus pneumoniae infection via activating innate leukocytes.
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DOI：
10.1038/mtm.2014.5
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发表时间：
2014
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影响因子：
--
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中科院分区：
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--
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肺炎球菌感染是社区获得性肺炎的主要原因。虽然1型干扰素-α (IFN-α)是一种众所周知的抗病毒细胞因子，但IFN-α在抗肺炎球菌宿主防御中的作用及其治疗潜力仍然知之甚少。我们通过小鼠转基因表达模型研究了这些问题。我们发现，在对照动物中，肺炎链球菌感染导致严重的体重减轻和过度的肺部炎症，并伴有细菌的快速生长。相比之下，在肺炎球菌感染前接受单剂量表达IFN-α的腺病毒载体的动物显示出对细菌复制和肺部炎症的快速有效控制，并改善了临床结果。IFN-α的增强保护作用是由于增加了中性粒细胞和巨噬细胞的活化，增加了活性氧和氮的释放以及细菌的杀伤。此外，我们发现，即使在肺炎球菌感染后给予基因转移载体，肺中IFN-α水平升高仍具有免疫保护作用。因此，我们的研究表明，经典的抗病毒1型IFN可以通过其对先天免疫细胞的激活作用来增强对肺炎球菌感染的免疫力。我们的研究结果对治疗使用IFN-α基因转移策略来对抗肺炎球菌感染具有重要意义。
Pneumococcal infections are the leading cause of community-acquired pneumonia. Although the type 1 interferon-α (IFN-α) is a well-known antiviral cytokine, the role of IFN-α in antipneumococcal host defense and its therapeutic potential remain poorly understood. We have investigated these issues by using a murine transgene expression model. We found that in control animals, Streptococcus pneumoniae infection caused severe weight loss and excessive lung inflammation, associated with rapid bacterial outgrowth. In contrast, the animals that received a single dose of an adenoviral vector expressing IFN-α prior to pneumococcal infection demonstrated rapid and effective control of bacterial replication and lung inflammation and improved clinical outcome. Enhanced protection by IFN-α was due to increased activation of neutrophils and macrophages with increased release of reactive oxygen and nitrogen species and bacterial killing. Furthermore, we found that raised levels of IFN-α in the lung remained immune protective even when the gene transfer vector was given at a time postpneumococcal infection. Our study thus shows that the classically antiviral type 1 IFN can be exploited for enhancing immunity against pneumococcal infection via its activating effects on innate immune cells. Our findings hold implications for the therapeutic use of IFN-α gene transfer strategies to combat pneumococcal infections.
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