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通过多重免疫组织化学鉴定 Q 热与动脉粥样硬化性腹主动脉瘤之间局部免疫细胞景观的差异。

Differences in local immune cell landscape between Q fever and atherosclerotic abdominal aortic aneurysms identified by multiplex immunohistochemistry.

机构信息

Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands.

Department of Internal Medicine, Division of Infectious Diseases and Radboud Center for Infectious Diseases, Radboud University Medical Centre, Nijmegen, Netherlands.

出版信息

Elife. 2022 Feb 9;11:e72486. doi: 10.7554/eLife.72486.

Abstract

BACKGROUND

Chronic Q fever is a zoonosis caused by the bacterium which can manifest as infection of an abdominal aortic aneurysm (AAA). Antibiotic therapy often fails, resulting in severe morbidity and high mortality. Whereas previous studies have focused on inflammatory processes in blood, the aim of this study was to investigate local inflammation in aortic tissue.

METHODS

Multiplex immunohistochemistry was used to investigate local inflammation in Q fever AAAs compared to atherosclerotic AAAs in aorta tissue specimen. Two six-plex panels were used to study both the innate and adaptive immune systems.

RESULTS

Q fever AAAs and atherosclerotic AAAs contained similar numbers of CD68 macrophages and CD3 T cells. However, in Q fever AAAs, the number of CD68CD206 M2 macrophages was increased, while expression of GM-CSF was decreased compared to atherosclerotic AAAs. Furthermore, Q fever AAAs showed an increase in both the number of CD8 cytotoxic T cells and CD3CD8FoxP3 regulatory T cells. Finally, Q fever AAAs did not contain any well-defined granulomas.

CONCLUSIONS

These findings demonstrate that despite the presence of pro-inflammatory effector cells, persistent local infection with is associated with an immune-suppressed microenvironment.

FUNDING

This work was supported by SCAN consortium: European Research Area - CardioVascualar Diseases (ERA-CVD) grant [JTC2017-044] and TTW-NWO open technology grant [STW-14716].

摘要

背景

慢性 Q 热是一种由细菌引起的动物传染病,可表现为腹主动脉瘤(AAA)感染。抗生素治疗往往失败,导致严重的发病率和高死亡率。虽然以前的研究集中在血液中的炎症过程,但本研究的目的是研究主动脉组织中的局部炎症。

方法

采用多重免疫组织化学方法比较 Q 热性 AAA 与动脉粥样硬化性 AAA 主动脉组织标本中的局部炎症。使用两个六聚体面板研究固有和适应性免疫系统。

结果

Q 热性 AAA 和动脉粥样硬化性 AAA 中 CD68 巨噬细胞和 CD3 T 细胞的数量相似。然而,在 Q 热性 AAA 中,与动脉粥样硬化性 AAA 相比,CD68CD206 M2 巨噬细胞的数量增加,而 GM-CSF 的表达减少。此外,Q 热性 AAA 中 CD8 细胞毒性 T 细胞和 CD3CD8FoxP3 调节性 T 细胞的数量均增加。最后,Q 热性 AAA 中没有形成明确的肉芽肿。

结论

这些发现表明,尽管存在促炎效应细胞,但持续存在的感染与局部免疫抑制微环境有关。

资金

这项工作得到了 SCAN 联盟的支持:欧洲研究区心血管疾病(ERA-CVD)资助[JTC2017-044]和 TTW-NWO 开放式技术资助[STW-14716]。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bca/8871373/4101c0ff87ca/elife-72486-fig1.jpg

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