Oliveira Flamélia Carla Silva, Pessoa Wallace Felipe Blohem, Mares Joise Hander, Freire Herbert Pina Silva, Souza Ednara Almeida de, Pirovani Carlos Priminho, Romano Carla Cristina
Department of Biological Sciences, Laboratory of Immunology, Center of Biotechnology and Genetics, State University of Santa Cruz, Ilhéus, Bahia, Brazil.
Department of Biological Sciences, Proteomics Laboratory, Biotechnology and Genetics Center, State University of Santa Cruz, Ilhéus, Bahia, Brazil.
Rev Iberoam Micol. 2021 Oct-Dec;38(4):159-167. doi: 10.1016/j.riam.2020.09.006. Epub 2021 Nov 19.
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.
The objective of this study was to identify differentially expressed proteins during the interaction between Paracoccidioides lutzii Pb01 strain and human U937 monocytes.
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.
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.
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.
副球孢子菌属真菌是副球孢子菌病的病原体，这是一种在拉丁美洲高度流行的真菌病。人类通过吸入分生孢子而感染，分生孢子随后会转变为酵母形式。在这种情况下，巨噬细胞是重要的防线，有助于识别和呈递抗原，以及产生活性氧以抑制真菌扩散。
本研究的目的是鉴定鲁氏副球孢子菌Pb01菌株与人类U937单核细胞相互作用过程中差异表达的蛋白质。
二维电泳结合质谱分析，用于评估鲁氏副球孢子菌（Pb01）与U937单核细胞相互作用的差异蛋白质组图谱。
能够鉴定出Pb01单独存在时以及与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能量产生的真菌代谢直接相关，例如甘油醛-3-磷酸脱氢酶，以及细胞内对单核细胞的适应性。参与氧化应激反应的抗氧化蛋白，如过氧化物酶、细胞色素和过氧化物酶，在与单核细胞相互作用时表达量更高，表明它们与吞噬细胞内的生存机制有关。我们还鉴定出12种在与真菌相互作用前后单核细胞中差异表达的蛋白质；鉴定出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，如乙二醛酶1。
对鲁氏副球孢子菌分离株的蛋白质组学研究结果是新颖的，模拟了人类感染中发生的体外情况。此外，鉴定出的蛋白质可能有助于理解真菌与单核细胞的相互作用以及副球孢子菌病的发病机制。
