Abstract
Extracellular vesicles (EVs) loaded with proteins, nucleic acids, membrane lipids, and other virulence factors could participate in pathogenic processes in some fungi such as Cryptococcus neoformans and Candida albicans. However, the specific characteristics of EVs derived from Talaromyces marneffei (TM) still have not been figured out yet. In the present study, it has been observed that TM-derived EVs were a heterogeneous group of nanosized membrane vesicles (30–300 nm) under nanoparticle tracking analysis and transmission electron microscopy. The DiI-labeled EVs could be taken up by RAW 264.7 macrophage cells. Incubation of EVs with macrophages would result in increased expression levels of reactive oxygen species, nitric oxide, and some inflammatory factors including interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor. Furthermore, the expression of co-stimulatory molecules (CD80, CD86, and MHC-II) was also increased in macrophages stimulated with EVs. The level of inflammatory factors secreted by macrophages showed a significant decrease when EVs were hydrolyzed by protease, while that of DNA and RNA hydrolase treatment remained unchanged. Subsequently, some virulence factors in EVs including heat shock protein, mannoprotein 1, and peroxidase were determined by liquid chromatography–tandem mass spectrometry. Taken together, our results indicated that the TM-derived EVs could mediate inflammatory response and its protein would play a key role in regulating the function of RAW 264.7 macrophage cells.
Highlights
Talaromyces marneffei (TM, formerly known as Penicillium marneffei) is an important pathogenic fungus prevalent in Southeast Asia such as Thailand, northeastern India, Vietnam, and southern China (Vanittanakom et al, 2002; Jiang et al, 2019a)
The specific pathogenesis of TM has not been fully figured out, and it needed to be investigated from a new perspective
Extracellular vesicles could act as a carriage with a lipid bilayer-enclosed structure to encapsulate numerous active molecules biologically, and taking EVs from fungi as example, it could transport some important molecules to the extracellular environment, mediating further processes
Summary
Talaromyces marneffei (TM, formerly known as Penicillium marneffei) is an important pathogenic fungus prevalent in Southeast Asia such as Thailand, northeastern India, Vietnam, and southern China (Vanittanakom et al, 2002; Jiang et al, 2019a). TM is a temperature-dependent diphasic fungus, and its highly contagious filamentous form at 25◦C can convert into a pathogenic yeast form at 37◦C (Andrianopoulos, 2002). It can cause an opportunistic infection, mainly spreading within immunodeficient populations such as HIV patients in the past few decades (Gugnani et al, 2004). With the increased use of immunosuppressants such as anti-IFN-γ in organ transplant rejection reactions and autoimmune diseases, the number of individuals with non-AIDS-related infection caused by TM is on the rise (Chan et al, 2016; Yu et al, 2018). Its specific pathogenic mechanism remains to be further elucidated
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