α1-抗胰蛋白酶通过刺激真菌丝状化影响宿主-病原体与白色念珠菌的先天相互作用。

IF 5.5 1区 农林科学 Q1 IMMUNOLOGY
Virulence Pub Date : 2024-12-01 Epub Date: 2024-04-10 DOI:10.1080/21505594.2024.2333367
Martin Jaeger, Axel Dietschmann, Sophie Austermeier, Sude Dinçer, Pauline Porschitz, Larsen Vornholz, Ralph J A Maas, Evelien G G Sprenkeler, Jürgen Ruland, Stefan Wirtz, Tania Azam, Leo A B Joosten, Bernhard Hube, Mihai G Netea, Charles A Dinarello, Mark S Gresnigt
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引用次数: 0

摘要

我们的免疫系统拥有复杂的机制来应对入侵的微生物,而病原体则采取各种策略来应对宿主免疫系统带来的威胁。人类血浆蛋白α1-抗胰蛋白酶(AAT)具有多种免疫调节特性,既能防止免疫病理,又能提高宿主的抗微生物防御能力。遗传关联表明 AAT 在念珠菌血症(ICU 中最常见的真菌血液感染)中发挥作用,但人们对 AAT 如何影响念珠菌与免疫系统之间的相互作用知之甚少。我们观察到,AAT 会诱导真菌转录重编程,这与细胞壁重塑和丝状抑制因子下调有关。这突出表明,真菌对宿主蛋白AAT的适应可不同程度地决定与先天性免疫细胞相遇的结果,要么有助于提高免疫识别能力,要么有助于真菌免疫逃逸。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Alpha1-antitrypsin impacts innate host-pathogen interactions with Candida albicans by stimulating fungal filamentation.

Our immune system possesses sophisticated mechanisms to cope with invading microorganisms, while pathogens evolve strategies to deal with threats imposed by host immunity. Human plasma protein α1-antitrypsin (AAT) exhibits pleiotropic immune-modulating properties by both preventing immunopathology and improving antimicrobial host defence. Genetic associations suggested a role for AAT in candidemia, the most frequent fungal blood stream infection in intensive care units, yet little is known about how AAT influences interactions between Candida albicans and the immune system. Here, we show that AAT differentially impacts fungal killing by innate phagocytes. We observed that AAT induces fungal transcriptional reprogramming, associated with cell wall remodelling and downregulation of filamentation repressors. At low concentrations, the cell-wall remodelling induced by AAT increased immunogenic β-glucan exposure and consequently improved fungal clearance by monocytes. Contrastingly, higher AAT concentrations led to excessive C. albicans filamentation and thus promoted fungal immune escape from monocytes and macrophages. This underscores that fungal adaptations to the host protein AAT can differentially define the outcome of encounters with innate immune cells, either contributing to improved immune recognition or fungal immune escape.

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来源期刊
Virulence
Virulence IMMUNOLOGY-MICROBIOLOGY
CiteScore
9.20
自引率
1.90%
发文量
123
审稿时长
6-12 weeks
期刊介绍: Virulence is a fully open access peer-reviewed journal. All articles will (if accepted) be available for anyone to read anywhere, at any time immediately on publication. Virulence is the first international peer-reviewed journal of its kind to focus exclusively on microbial pathogenicity, the infection process and host-pathogen interactions. To address the new infectious challenges, emerging infectious agents and antimicrobial resistance, there is a clear need for interdisciplinary research.
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