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肺炎支原体与社区获得性呼吸窘迫综合征毒素的免疫病理效应。灵长类动物模型。

The Immunopathologic Effects of Mycoplasma pneumoniae and Community-acquired Respiratory Distress Syndrome Toxin. A Primate Model.

作者信息

Maselli Diego J, Medina Jorge L, Brooks Edward G, Coalson Jacqueline J, Kannan Thirumalai R, Winter Vicki T, Principe Molly, Cagle Marianna P, Baseman Joel B, Dube Peter H, Peters Jay I

机构信息

1 Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine.

2 Department of Microbiology and Immunology.

出版信息

Am J Respir Cell Mol Biol. 2018 Feb;58(2):253-260. doi: 10.1165/rcmb.2017-0006OC.

Abstract

Mycoplasma pneumoniae infection has been linked to poor asthma outcomes. M. pneumoniae produces an ADP-ribosylating and vacuolating toxin called community-acquired respiratory distress syndrome (CARDS) toxin that has a major role in inflammation and airway dysfunction. The objective was to evaluate the immunopathological effects in primates exposed to M. pneumoniae or CARDS toxin. A total of 13 baboons were exposed to M. pneumoniae or CARDS toxin. At Days 7 and 14, BAL fluid was collected and analyzed for cell count, percent of each type of cell, CARDS toxin by PCR, CARDS toxin by antigen capture, eosinophilic cationic protein, and cytokine profiles. Serum IgM, IgG, and IgE responses to CARDS toxin were measured. All animals had a necropsy for analysis of the histopathological changes on lungs. No animal developed signs of infection. The serological responses to CARDS toxin were variable. At Day 14, four of seven animals exposed to M. pneumoniae and all four animals exposed to CARDS toxin developed histological "asthma-like" changes. T cell intracellular cytokine analysis revealed an increasing ratio of IL-4/IFN-γ over time. Both M. pneumoniae and CARDS toxin exposure resulted in similar histopathological pulmonary changes, suggesting that CARDS toxin plays a major role in the inflammatory response.

摘要

肺炎支原体感染与哮喘不良预后有关。肺炎支原体产生一种名为社区获得性呼吸窘迫综合征(CARDS)毒素的ADP核糖基化和空泡化毒素,该毒素在炎症和气道功能障碍中起主要作用。目的是评估暴露于肺炎支原体或CARDS毒素的灵长类动物的免疫病理效应。总共13只狒狒暴露于肺炎支原体或CARDS毒素。在第7天和第14天,收集支气管肺泡灌洗(BAL)液并分析细胞计数、每种细胞类型的百分比、通过聚合酶链反应(PCR)检测的CARDS毒素、通过抗原捕获检测的CARDS毒素、嗜酸性阳离子蛋白和细胞因子谱。检测血清对CARDS毒素的IgM、IgG和IgE反应。所有动物均进行尸检以分析肺部的组织病理学变化。没有动物出现感染迹象。对CARDS毒素的血清学反应各不相同。在第14天,七只暴露于肺炎支原体的动物中有四只以及所有四只暴露于CARDS毒素的动物出现了组织学上的“哮喘样”变化。T细胞细胞内细胞因子分析显示,随着时间的推移,IL-4/IFN-γ的比例增加。暴露于肺炎支原体和CARDS毒素均导致类似的肺部组织病理学变化,这表明CARDS毒素在炎症反应中起主要作用。

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