Department of Cell Biology, University of Brasília, Brasília, Brazil.
Department of Pathology, Federal University of Paraná, Curitiba, Brazil.
Front Cell Infect Microbiol. 2022 Jun 9;12:879018. doi: 10.3389/fcimb.2022.879018. eCollection 2022.
Chromoblastomycosis (CBM) is a chronic cutaneous and subcutaneous mycosis caused by black, dimorphic, and filamentous fungi of the family, such as species of the genus . These fungi can switch between the saprophytic forms (conidia and hyphae) and the pathogenic form, the muriform cells (MCs), which is considered an essential mechanism for fungal virulence. Nearly all types of cells can produce membranous structures formed by a lipid bilayer that communicate extracellularly with other cells, known as "extracellular vesicles" (EVs), which may act as virulence factors, as observed for several species of pathogenic fungi. Our findings demonstrated for the first time that , and produce EVs in response to nutritional conditions. The EVs varied in sterol and protein contents, size, and morphology. Moreover, the EVs induced different cytokine and nitric oxide release patterns by bone marrow-derived macrophages (BMDMs). The EVs activated IL-1β production, possibly acting as the first signal in inflammasome activation. Unlike the pathogenic species, the EVs isolated from did not significantly stimulate TNF and IL-10 production in general. Overall, these results demonstrated that different species of produce EVs capable of modulating pro- and anti-inflammatory cytokine and nitric oxide production by BMDMs and that growth conditions affected the immunomodulatory capacities of the EVs as well as their size, content, and morphology.
着色芽生菌病（CBM）是一种由暗色、二相和丝状真菌引起的慢性皮肤和皮下真菌感染，这些真菌可在腐生形式（分生孢子和菌丝）和致病性形式，即多形细胞（MCs）之间转换，这被认为是真菌毒力的一个重要机制。几乎所有类型的细胞都可以产生由脂质双层形成的膜状结构，这些结构与其他细胞进行细胞外通讯，称为“细胞外囊泡”（EVs），这可能作为毒力因子起作用，正如几种致病性真菌所观察到的那样。我们的研究结果首次表明， 和 会根据营养条件产生 EVs。EVs 在甾醇和蛋白质含量、大小和形态上有所不同。此外，EVs 诱导骨髓来源的巨噬细胞（BMDMs）释放不同的细胞因子和一氧化氮。EVs 激活了 IL-1β 的产生，可能作为炎症小体激活的第一信号。与致病性物种不同，从 中分离的 EVs 通常不会显著刺激 TNF 和 IL-10 的产生。总体而言，这些结果表明，不同种 的 能够产生 EVs，调节 BMDMs 中促炎和抗炎细胞因子和一氧化氮的产生，并且生长条件影响 EVs 的免疫调节能力以及其大小、内容物和形态。
