Antifungal Activity, Structural Stability, and Immunomodulatory Effects on Human Immune Cells of Defensin from the Lentil Lens culinaris

Abstract

An increase in the frequency of mycoses and spreading of multidrug-resistant fungal pathogens necessitates the search for new antifungal agents. Earlier, we isolated the novel defensin from lentil Lens culinaris seeds, designated as Lc-def, which inhibited the growth of phytopathogenic fungi. Here, we studied an antifungal activity of Lc-def against human pathogenic Candida species, structural stability of the defensin, and its immunomodulatory effects that may help to prevent fungal infection. We showed that Lc-def caused 50% growth inhibition of clinical isolates of Candida albicans, C. krusei, and C. glabrata at concentrations of 25–50 μM, but was not toxic to different human cells. The lentil defensin was resistant to proteolysis by C. albicans and was not cleaved during simulated gastroduodenal digestion. By using the multiplex xMAP assay, we showed for the first time for plant defensins that Lc-def increased the production of such essential for immunity to candidiasis pro-inflammatory cytokines as IL-12 and IL-17 at the concentration of 2 μM. Thus, we hypothesized that the lentil Lc-def and plant defensins in general may be effective in suppressing of mucocutaneous candidiasis due to their antifungal activity, high structural stability, and ability to activate a protective immune response.

Antifungal Plant Defensins as an Alternative Tool to Combat Candidiasis

“…Real-time PCR, the multiplex xMAP assay [49] Macrophages Increase in the production of inflammatory chemokines MIG, MCP-1, and MIP-1…”

“…Plant defensins, unlike many other classes of AMPs, demonstrate high stability, due to their compact structure stabilized by disulfide bonds. Plant defensins can withstand high temperatures and boiling [ 37 , 48 ], and retain their structure in strongly acidic solutions [ 48 , 49 ]. These peptides are resistant to proteolytic enzymes of the human gastrointestinal tract [ 49 , 50 ] and serum [ 37 ] and are not degraded by proteases of C. albicans [ 49 ].…”

“…It has been shown that Psd1, as well as Lc-def, affects the production of a broad range of both pro- and anti-inflammatory cytokines/chemokines and growth factors by different types of immune cells ( Table 3 ). It is interesting to note that Psd1, as well as Lc-def, increases almost the same immune factors in both cultures, monocyte-derived dendritic cells (moDCs), and monocytes [ 49 , 79 ]. Moreover, Lc-def induces the production of IL-17 by regulatory CD4 + FoxP3 + T cells (Tregs), which play a critical role in anti-candida immunity [ 49 ].…”

“…It is interesting to note that Psd1, as well as Lc-def, increases almost the same immune factors in both cultures, monocyte-derived dendritic cells (moDCs), and monocytes [ 49 , 79 ]. Moreover, Lc-def induces the production of IL-17 by regulatory CD4 + FoxP3 + T cells (Tregs), which play a critical role in anti-candida immunity [ 49 ]. Peptide solyC affects THP-1 stimulated with lipopolysaccharide but has no effect on unstimulated cells [ 110 ].…”

Risk of candidiasis associated with interleukin-17 inhibitors: Implications and management

“…IL-17 stimulates the production of various chemokines that recruit immune cells to the infection site, thus boosting their ability to engulf and eliminate the attacking Candida species (Li et al 2019 ). IL-17 also stimulates the production of antimicrobial peptides, such as cathelicidins and defensins, which have potent fungicidal activity against Candida ( Figure 1 : Model) (Finkina et al 2022 ). Thus, the absence of IL-17 or its signalling pathways can result in fatal and chronic Candida infections (Tangye and Puel 2023 ).…”