小鼠出生早期肺炎链球菌感染对成年期相同细菌性抗原诱导的哮喘严重程度的影响

doi:10.3969/j.issn.1006-7795.2023.02.005

首都医科大学学报 ›› 2023, Vol. 44 ›› Issue (2): 212-220.doi: 10.3969/j.issn.1006-7795.2023.02.005

• 呼吸系统疾病免疫学研究进展 • 上一篇下一篇

小鼠出生早期肺炎链球菌感染对成年期相同细菌性抗原诱导的哮喘严重程度的影响

彭丹^1,2，庞洁¹，史一凡¹，崔乐乐¹，徐英杰¹，李艳³，崔烨¹，陈彦¹，袁慧慧¹，秦啸峰¹，吕喆¹，王炜¹，孙英^1*

1. 首都医科大学基础医学院免疫学系，北京 100069； 2. 成都市第三人民医院过敏与精准医学实验室，成都 610014; 3.首都医科大学附属北京同仁医院耳鼻咽喉头颈外科，北京100730

收稿日期:2023-01-24 出版日期:2023-04-21 发布日期:2023-04-17
通讯作者: 孙英 E-mail:ying.sun@ccmu.edu.cn
基金资助:
国家自然科学基金(82071805, 82090013, 81971510, 81770049)，北京市属高校高水平教师队伍建设支持计划高水平创新团队建设计划项目(IDHT20190510）

Streptococcus pneumoniae infection at early stage of life affect the severity of asthma induced by exposure to the same bacterial antigens in adulthood

Peng Dan^1,2, Pang Jie¹, Shi Yifan¹, Cui Lele¹, Xu Yingjie¹, Li Yan³, Cui Ye¹, Chen Yan¹, Yuan Huihui¹, Qin Xiaofeng¹, Lyu Zhe¹, Wang Wei¹, Sun Ying^1*

1. Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China; 2. Laboratory of Allergy and Precision Medicine, the Third People's Hospital of Chengdu, Chengdu 610014, China; 3. Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China

Received:2023-01-24 Online:2023-04-21 Published:2023-04-17
Supported by:
This study was supported by National Natural Science Foundation of China (82071805, 82090013,81971510, 81770049), the Beijing Municipal High Level of Teacher Team Construction in Colleges and Universities Support Plan High Level Innovation Teams Construction Projects (IDHT20190510).

摘要/Abstract

摘要： 目的探讨小鼠出生早期气道感染肺炎链球菌(Streptococcus pneumoniae，SP）后，成年期暴露于相同细菌性抗原时对哮喘发生发展的影响及机制研究，为过敏性哮喘防治提供新的研究方向。方法 1周龄WT BALB/c小鼠滴鼻感染SP，5周后反复滴鼻灭活SP菌体及白细胞介素-33（interleukin-33, IL-33）+灭活SP菌体，检测小鼠气道高反应性(airway hyperresponsiveness, AHR)，明确气道/肺部炎性细胞浸润情况及炎症改变；检测血清中免疫球蛋白E(immunoglobulin E, IgE）及SP特异性IgE、IgG浓度和肺组织匀浆中细胞因子表达水平；最后明确肺组织中辅助性T细胞（T helper cell, Th）亚群（Th1、Th2、Th17）和固有淋巴细胞（innate lymphoid cells, ILC）亚群（ILC1、ILC2、ILC3）细胞数变化情况。结果出生早期SP感染后，成年期单独暴露于相同细菌性抗原未能诱导出哮喘样病理改变；在IL-33存在下，虽然出生早期SP感染后成年期暴露于相同细菌性抗原依然引起以2型细胞因子增加为主的混合性炎症，但与未经感染组相比，实验组小鼠的气道高反应性下降；支气管肺泡灌洗液（bronchoalveolar lavage fluid, BALF）总细胞计数下降；肺组织中嗜酸性粒细胞浸润减少；黏液分泌明显减少；平滑肌增生减轻；血清中IgE明显下降，然而SP菌体特异性IgE、IgG明显升高；多种细胞因子减少；抑制炎症因子(IL-10）明显升高；虽然ILC2细胞数量明显升高，但Th1、Th2、Th17及ILC1细胞数量明显下降。结论出生早期SP感染可降低成年期小鼠暴露于相同细菌性抗原时诱发的哮喘的严重程度。

关键词: 出生早期感染, 肺炎链球菌, IL-33, 细菌性抗原, 哮喘

Abstract: Objective To investigate the influence and mechanisms of infection with Streptococcus pneumoniae(SP)at early stage of life and late exposure to the same bacterial antigens on the occurrence and development of asthma.Methods Mice (one week old of BALB/c background) were infected with SP, then 5 weeks later challenged intranasally with inactivate SP bacteria and interleukin-33 (IL-33)+inactivated SP bacteria to establish model. Lung function and airways hyperresponsiveness (AHR), total cellular and differential counts in bronchoalveolar lavage fluid (BALF) and lungs were measured to evaluate the inflammatory cell infiltration and inflammatory changes in the airways/lungs.The expression levels of IgE and SP specific IgE and IgG in serum, as well as the expression levels of various cytokines in lung homogenates were detected with ELISA.The number of T helper cell (Th) subgroup (Th1, Th2, Th17) and innate lymphoid cells (ILC1, ILC2, ILC3) were measure with flow cytometry. Results Early-life airways infection with SP and repeated exposure to the same bacterial antigen alone in adulthood failed to induce asthma-like pathological changes. In the presence of IL-33, early-life airways infection with SP and repeated exposure to the same bacterial antigen attenuated asthma-like pathological changes, including the dereased AHR, inflammatory cellular infiltration of the airways, secretion of mucus and smooth muscle hyperplasia in lung tissue, serum concentrations of IgE and concentrations of Th2-type cytokines, numbers of activated Th1, Th2, Th17 and ILC1 cells in the lung tissues, but an increased IL-10 expression, compared with those mice without SP infection in early life. Conclusion Early-life airways infection with SP attenuted the severity of asthma induced by exposure to the same bacterial antigens in adulthood.

Key words: early birth infections, Streptococcus pneumoniae, interleukin-33 (IL-33), bacterial antigens, asthma

中图分类号:

R392

彭丹, 庞洁, 史一凡, 崔乐乐, 徐英杰, 李艳崔, 烨陈彦, 袁慧慧, 秦啸峰, 吕喆, 王炜, 孙英. 小鼠出生早期肺炎链球菌感染对成年期相同细菌性抗原诱导的哮喘严重程度的影响[J]. 首都医科大学学报, 2023, 44(2): 212-220.

Peng Dan, Pang Jie, Shi Yifan, Cui Lele, Xu Yingjie, Li Yan, Cui Ye, Chen Yan, Yuan Huihui, Qin Xiaofeng, Lyu Zhe, Wang Wei, Sun Ying. Streptococcus pneumoniae infection at early stage of life affect the severity of asthma induced by exposure to the same bacterial antigens in adulthood[J]. Journal of Capital Medical University, 2023, 44(2): 212-220.

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小鼠出生早期肺炎链球菌感染对成年期相同细菌性抗原诱导的哮喘严重程度的影响

Streptococcus pneumoniae infection at early stage of life affect the severity of asthma induced by exposure to the same bacterial antigens in adulthood

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