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肽蕈醇甘露聚糖:棘孢木霉和小棘孢霉的表面真菌糖复合物及其被巨噬细胞的识别。

Peptidorhamanomannan: A surface fungal glycoconjugate from Scedosporium aurantiacum and Scedosporium minutisporum and its recognition by macrophages.

机构信息

Instituto de Microbiologia Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro (UFRJ), Bloco I, Ilha do Fundão, 21941-970, Rio de Janeiro, RJ, Brazil.

Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná (UFPR), 81531-980, Curitiba, PR, Brazil.

出版信息

Med Mycol. 2021 May 4;59(5):441-452. doi: 10.1093/mmy/myaa065.

DOI:10.1093/mmy/myaa065
PMID:32766889
Abstract

The genus Scedosporium is composed of clinically relevant fungal species, such as Scedosporium aurantiacum, Scedosporium apiospermum, and Scedosporium boydii. Surface molecules have been described that play crucial roles in fungi-macrophage interaction, and many of them are pathogen-associated molecular patterns (PAMPs). The present study aims to characterize peptidoglycans obtained from Scedosporium aurantiacum and Scedosporium minutisporum, a clinical and an environmental isolate, respectively, and compare their roles in pathogen-host interaction. Both molecules were characterized as peptidorhamnomannans (PRMs), similar to what has been already described for other Scedosporium species. Rabbit immune sera obtained by injecting whole cells from each species recognized both fungal cells and purified PRMs, suggesting that a cross-reaction occur between both fungi. Immunofluorescent microscopy revealed that PRMs are exposed on fungal surface. Prior incubation of purified molecules with immune sera before adding to cells led to loss of fluorescent, indicating that PRM is a major molecule recognized by immune sera. Fungi-macrophage interaction revealed that S. aurantiacum is able to survive more inside phagocytic cells than S. minutisporum, and PRM from both fungi plays a role in phagocytosis when the purified molecule is pre-incubated with macrophage. In addition, PRM induce nitric oxide release by macrophages. Our data indicate that PRM is an important PAMP exposed on fungal surface with the potential of immune modulation.

摘要

棘孢木霉属由临床相关真菌物种组成,如橘青霉、枝顶孢霉和鞘孢菌。已经描述了在真菌与巨噬细胞相互作用中起关键作用的表面分子,其中许多是病原体相关分子模式 (PAMP)。本研究旨在表征分别从临床分离株棘孢菌和环境分离株小孢枝顶孢菌中获得的肽聚糖,并比较它们在病原体-宿主相互作用中的作用。这两种分子均被鉴定为肽-鼠李糖甘露聚糖 (PRM),与其他棘孢菌属物种已描述的结构相似。通过注射来自每个物种的完整细胞来免疫兔获得的免疫血清识别两种真菌细胞和纯化的 PRM,表明两种真菌之间发生了交叉反应。免疫荧光显微镜显示 PRM 暴露在真菌表面。在将纯化的分子与细胞共孵育之前,用免疫血清预先孵育会导致荧光丧失,表明 PRM 是免疫血清识别的主要分子。真菌-巨噬细胞相互作用表明,与小孢枝顶孢菌相比,橘青霉在吞噬细胞内更能存活,并且当将纯化的分子与巨噬细胞预孵育时,来自两种真菌的 PRM 在吞噬作用中起作用。此外,PRM 诱导巨噬细胞释放一氧化氮。我们的数据表明 PRM 是一种暴露在真菌表面的重要 PAMP,具有免疫调节的潜力。

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