曲霉菌分生孢子诱导的炎症反应依赖于补体激活--全血模型的启示。

IF 4.7 3区 医学 Q2 IMMUNOLOGY
Journal of Innate Immunity Pub Date : 2024-01-01 Epub Date: 2024-05-20 DOI:10.1159/000539368
Beatrice Fageräng, Maximilian Peter Götz, Leon Cyranka, Corinna Lau, Per H Nilsson, Tom Eirik Mollnes, Peter Garred
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引用次数: 0

摘要

引言我们的目的是在先天性免疫激活的全血模型中阐明曲霉菌分生孢子的炎症反应,并将其与大肠杆菌的炎症反应进行比较:方法:我们利用人体利血平全血模型,通过测量 sC5b-9 复合物和评估 CD11b 表达来分析补体和白细胞活化。细胞因子的定量采用了 27 种多重系统。此外,还从全血中选择性地移除细胞并抑制 C3、C5 和 CD14:结果:我们的研究结果表明,烟曲霉培养后 sC5b-9 和 CD11b 明显升高。有 13 种细胞因子(TNF、IL-1β、IL-1ra、IL-4、IL-6、IL-8、IL-17、IFNγ、MCP-1、MIP-1α、MIP-1β、FGF-basic 和 G-CSF)水平升高。与大肠杆菌相比,在烟曲霉分生孢子中观察到的细胞因子释放和 CD11b 表达水平普遍较低。值得注意的是,除 MCP-1 外,单核细胞对所有细胞因子的释放都有作用。研究发现,IL-1ra 既依赖于单核细胞,也依赖于粒细胞。使用 C3 和 CD14 抑制剂进行预抑制可减少六种细胞因子(TNF、IL-1β、IL-6、IL-8、MIP-1α 和 MIP-1β)的释放模式,而 C5 抑制剂的影响极小:结论:烟曲霉菌分生孢子诱导的补体激活与大肠杆菌相当,而CD11b的表达和细胞因子的释放较低,这说明这些病原体之间的炎症反应不同。抑制补体C3可减少细胞因子的释放,这表明补体在烟曲霉免疫中起着C3水平的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Inflammatory Response Induced by Aspergillus fumigatus Conidia Is Dependent on Complement Activation: Insight from a Whole Blood Model.

Introduction: We aimed to elucidate the inflammatory response of Aspergillus fumigatus conidia in a whole-blood model of innate immune activation and to compare it with the well-characterized inflammatory reaction to Escherichia coli.

Methods: Employing a human lepirudin whole-blood model, we analyzed complement and leukocyte activation by measuring the sC5b-9 complex and assessing CD11b expression. A 27-multiplex system was used for quantification of cytokines. Selective cell removal from whole blood and inhibition of C3, C5, and CD14 were also applied.

Results: Our findings demonstrated a marked elevation in sC5b-9 and CD11b post-A. fumigatus incubation. Thirteen cytokines (TNF, IL-1β, IL-1ra, IL-4, IL-6, IL-8, IL-17, IFNγ, MCP-1, MIP-1α, MIP-1β, FGF-basic, and G-CSF) showed increased levels. A generally lower level of cytokine release and CD11b expression was observed with A. fumigatus conidia than with E. coli. Notably, monocytes were instrumental in releasing all cytokines except MCP-1. IL-1ra was found to be both monocyte and granulocyte-dependent. Pre-inhibiting with C3 and CD14 inhibitors resulted in decreased release patterns for six cytokines (TNF, IL-1β, IL-6, IL-8, MIP-1α, and MIP-1β), with minimal effects by C5-inhibition.

Conclusion: A. fumigatus conidia induced complement activation comparable to E. coli, whereas CD11b expression and cytokine release were lower, underscoring distinct inflammatory responses between these pathogens. Complement C3 inhibition attenuated cytokine release indicating a C3-level role of complement in A. fumigatus immunity.

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来源期刊
Journal of Innate Immunity
Journal of Innate Immunity 医学-免疫学
CiteScore
10.50
自引率
1.90%
发文量
35
审稿时长
7.5 months
期刊介绍: The ''Journal of Innate Immunity'' is a bimonthly journal covering all aspects within the area of innate immunity, including evolution of the immune system, molecular biology of cells involved in innate immunity, pattern recognition and signals of ‘danger’, microbial corruption, host response and inflammation, mucosal immunity, complement and coagulation, sepsis and septic shock, molecular genomics, and development of immunotherapies. The journal publishes original research articles, short communications, reviews, commentaries and letters to the editors. In addition to regular papers, some issues feature a special section with a thematic focus.
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