Background

Fungi of the genus Paracoccidioides are the etiological agents of paracoccidioidomycosis, a highly prevalent mycosis in Latin America. Infection in humans occurs by the inhalation of conidia, which later revert to the form of yeast. In this context, macrophages are positioned as an important line of defense, assisting in the recognition and presentation of antigens, as well as producing reactive oxygen species that inhibit fungal spreading.

Aims

The objective of this study was to identify differentially expressed proteins during the interaction between Paracoccidioides lutzii Pb01 strain and human U937 monocytes.

Methods

Two-dimensional electrophoresis, combined with mass spectrometry, was used to evaluate the differential proteomic profiles of the fungus P. lutzii (Pb01) interacting with U937 monocytes.

Results

It was possible to identify 25 proteins differentially expressed by Pb01 alone and after interacting with U937 monocytes. Most of these proteins are directly associated with fungal metabolism for energy generation, such as glyceraldehyde-3-phosphate dehydrogenase, and intracellular adaptation to monocytes. Antioxidant proteins involved in the response to oxidative stress, such as peroxiredoxin, cytochrome, and peroxidase, were expressed in greater quantity in the interaction with monocytes, suggesting their association with survival mechanisms inside phagocytic cells. We also identified 12 proteins differentially expressed in monocytes before and after the interaction with the fungus; proteins involved in the reorganization of the cytoskeleton, such as vimentin, and proteins involved in the response to oxidative stress, such as glioxalase 1, were identified.

Conclusions

The results of this proteomic study of a P. lutzii isolate are novel, mimicking in vitro what occurs in human infections. In addition, the proteins identified may aid to understand fungal–monocyte interactions and the pathogenesis of paracoccidioidomycosis.

中文翻译：

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Paracoccidioides lutzii 与人单核细胞相互作用中差异表达的蛋白质

背景

副球孢子菌属真菌是副球孢子菌病的病原体，副球孢子菌病是拉丁美洲高度流行的真菌病。人类感染通过吸入分生孢子而发生，分生孢子后来恢复为酵母形式。在这种情况下，巨噬细胞被定位为重要的防线，协助识别和呈递抗原，以及产生抑制真菌传播的活性氧。

宗旨

本研究的目的是之间的交互期间，以确定差异表达的蛋白质副球孢子lutzii PB01应变和人U937单核细胞。

方法

二维电泳结合质谱法用于评估与 U937 单核细胞相互作用的真菌P. lutzii (Pb01)的差异蛋白质组学特征。

结果

有可能鉴定单独由 Pb01 和与 U937 单核细胞相互作用后差异表达的 25 种蛋白质。这些蛋白质中的大多数与用于产生能量的真菌代谢直接相关，例如 3-磷酸甘油醛脱氢酶和细胞内对单核细胞的适应。参与对氧化应激反应的抗氧化蛋白，如过氧还蛋白、细胞色素和过氧化物酶，在与单核细胞的相互作用中表达量更大，表明它们与吞噬细胞内的生存机制有关。我们还鉴定了在与真菌相互作用前后在单核细胞中差异表达的 12 种蛋白质；参与细胞骨架重组的蛋白质，如波形蛋白，以及参与氧化应激反应的蛋白质，如胶质酶 1，

结论

这项对P. lutzii分离株的蛋白质组学研究的结果是新颖的，在体外模拟了人类感染中发生的情况。此外，鉴定出的蛋白质可能有助于了解真菌-单核细胞的相互作用和副球孢子菌病的发病机制。