Insight Into the Properties and Immunoregulatory Effect of Extracellular Vesicles Produced by Candida glabrata, Candida parapsilosis, and Candida tropicalis Biofilms

Abstract

Currently, non-<i>albicans Candida</i> species, including <i>C. tropicalis</i>, <i>C. glabrata</i>, and <i>C. parapsilosis</i>, are becoming an increasing epidemiological threat, predominantly due to the distinct collection of virulence mechanisms, as well as emerging resistance to antifungal drugs typically used in the treatment of candidiasis. They can produce biofilms that release extracellular vesicles (EVs), which are nanometric spherical structures surrounded by a lipid bilayer, transporting diversified biologically active cargo, that may be involved in intercellular communication, biofilm matrix production, and interaction with the host. In this work, we characterize the size and protein composition of these structures for three species of non-<i>albicans Candida</i> fungi forming biofilm, indicating considerable heterogeneity of the investigated population of fungal EVs. Examination of the influence of EVs on cytokine production by the human monocytic cell line THP-1 differentiated into macrophage-like cells revealed that the tested vesicles have a stimulating effect on the secretion of tumor necrosis factor α and interleukin 8, while they reduce the production of interleukin 10. This may indicate the proinflammatory nature of the effect of EVs produced by these species on the host immune cells. Moreover, it has been indicated that vesicles may be involved in <i>C. tropicalis</i> biofilm resistance to fluconazole and caspofungin. This reveals the important role of EVs not only in the physiology of <i>C. tropicalis</i>, <i>C. glabrata</i>, and <i>C. parapsilosis</i> fungi but also in the pathogenesis of infections associated with the production of fungal biofilm.