Neonatal Streptococcus pneumoniae infection may aggravate adulthood allergic airways disease in association with IL-17A.

Neonatal Streptococcus pneumoniae infection may aggravate adulthood allergic airways disease in association with IL-17A.
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DOI:
10.1371/journal.pone.0123010
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Fu Z
Fu Z
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yang B;Liu R;Yang T;Jiang X;Zhang L;Wang L;Wang Q;Luo Z;Liu E;Fu Z

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流行病学研究表明,生命早期的一些细菌定植或感染会增加随后发生哮喘的风险。然而,人们对生命早期细菌感染增加这种风险的机制知之甚少。本研究旨在探讨新生儿肺炎链球菌感染对成年哮喘发生的影响,并探讨其可能的机制。通过给新生(1周龄)雌性小鼠鼻内接种D39,建立非致死性肺炎链球菌肺部感染。小鼠在成年后接受卵清蛋白致敏和攻击,以诱发过敏性气道疾病(AAD)。 24 小时后,收集肺部和支气管肺泡灌洗液 (BALF) 以评估 AAD。新生儿肺炎链球菌感染加剧了 AAD 的成年标志特征,包括气道高反应性增强、气道中性粒细胞募集增加、Th17 细胞和白细胞介素 (IL)-17A 产生增加。通过腹膜内注射耗尽 IL-17A注射中和单克隆抗体可减少中性粒细胞向气道的募集,减轻气道炎症并降低气道高反应性。此外,IL-17A 耗竭部分恢复了干扰素-γ 的水平,但对 IL-5 或 IL-13 的释放没有影响。我们的数据表明,新生儿肺炎链球菌感染可能会促进成人哮喘的发生,并与 IL-17A 产生增加相关。
Epidemiologic studies have demonstrated that some bacteria colonization or infections in early-life increased the risk for subsequent asthma development. However, little is known about the mechanisms by which early-life bacterial infection increases this risk. The aim of this study was to investigate the effect of neonatal Streptococcus pneumoniae infection on the development of adulthood asthma, and to explore the possible mechanism. A non-lethal S. pneumoniae lung infection was established by intranasal inoculation of neonatal (1-week-old) female mice with D39. Mice were sensitized and challenged with ovalbumin in adulthood to induce allergic airways disease (AAD). Twenty-four hours later, the lungs and bronchoalveolar lavage fluid (BALF) were collected to assess AAD. Neonatal S. pneumoniae infection exacerbated adulthood hallmark features of AAD, with enhanced airway hyperresponsiveness and increased neutrophil recruitment into the airways, increased Th17 cells and interleukin (IL)-17A productions. Depletion of IL-17A by i.p. injection of a neutralizing monoclonal antibody reduced neutrophil recruitment into the airways, alleviated airway inflammation and decreased airway hyperresponsiveness. Furthermore, IL-17A depletion partially restored levels of inteferon-γ, but had no effect on the release of IL-5 or IL-13. Our data suggest that neonatal S. pneumoniae infection may promote the development of adulthood asthma in association with increased IL-17A production.
白介素17a介导获得的对肺炎球菌定殖的免疫力。
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