来自不同菌株的细胞外囊泡调节吞噬细胞功能并促进真菌持续存在。

Extracellular vesicles from Distinct Strains Modulate Phagocyte Function and Promote Fungal Persistence.

作者信息

Souza Taiane N, Valdez Alessandro F, Zimbres Ana Claudia G, Sena Bianca A G, Reis Flavia C G, Rodrigues Marcio L, Zamith-Miranda Daniel, Guimarães Allan J, Filardy Alessandra A, Nosanchuk Joshua D, Nimrichter Leonardo

机构信息

Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.

Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, New York 10461, United States.

出版信息

ACS Infect Dis. 2025 Aug 8;11(8):2342-2356. doi: 10.1021/acsinfecdis.5c00378. Epub 2025 Jul 13.

Abstract

Fungal extracellular vesicles (EVs) are lipid-bilayer compartments that transport a wide range of molecules, including proteins, polysaccharides, pigments, small metabolites, lipids, and RNA. In fungal pathogens, EVs harbor virulence factors as well as antigenic determinants that modulate the host immune response. In this work, we investigated the modulatory effects of EVs released by two phenotypically and genotypically distinct strains of (G-217B and G-184A) on bone marrow-derived macrophages (BMDMs) and bone marrow-derived dendritic cells (BMDCs). Both host cells internalized EVs, which appeared to elicit distinct functional responses. Treatment of BMDMs with EVs from either strain (EV and EV) increased IL-6 production with no significant changes in IL-10 levels. In contrast, BMDCs exposed with both EVs exhibited elevated levels of IL-6 and IL-10. Although EV treatment led to increased inducible nitric oxide synthase expression in BMDMs, it did not stimulate NO production. Remarkably, both EVs reduced the metabolic activity of phagocytes. Overnight exposure to EV enhanced the phagocytosis of yeasts by BMDMs; however, the phagolysosomal fusion was not affected. Notably, in DCs, EV enhanced both the uptake and the viability of G-217B yeasts. Furthermore, incubation of with its respective EVs promoted fungal growth, suggesting a self-stimulatory mechanism that may contribute to fungal persistence within host cells. Taken together, our results support the idea that EVs are modulators of host-pathogen interaction, influencing phagocyte function and potentially contributing to fungal virulence.

摘要

真菌细胞外囊泡(EVs)是脂质双层隔室,可运输多种分子,包括蛋白质、多糖、色素、小代谢物、脂质和RNA。在真菌病原体中,EVs含有毒力因子以及调节宿主免疫反应的抗原决定簇。在这项研究中,我们研究了两种表型和基因型不同的 (G - 217B和G - 184A)菌株释放的EVs对骨髓来源的巨噬细胞(BMDMs)和骨髓来源的树突状细胞(BMDCs)的调节作用。两种宿主细胞都内化了 EVs,这似乎引发了不同的功能反应。用来自任一菌株的EVs(EV 和EV)处理BMDMs可增加IL - 6的产生,而IL - 10水平无显著变化。相比之下,暴露于两种EVs的BMDCs表现出IL - 6和IL - 10水平升高。尽管EV处理导致BMDMs中诱导型一氧化氮合酶表达增加,但它并未刺激NO的产生。值得注意的是,两种EVs都降低了吞噬细胞的代谢活性。过夜暴露于EV增强了BMDMs对 酵母的吞噬作用;然而,吞噬溶酶体融合未受影响。值得注意的是,在DCs中,EV增强了G - 217B酵母的摄取和活力。此外, 与其各自的EVs共孵育促进了真菌生长,表明一种自我刺激机制可能有助于真菌在宿主细胞内持续存在。综上所述,我们的结果支持这样一种观点,即 EVs是宿主 - 病原体相互作用的调节剂,影响吞噬细胞功能并可能有助于真菌毒力。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索