Immunomodulatory Effects of the Pea Defensin Psd1 in the Caco-2/Immune Cells Co-Culture upon Candida albicans Infection

Abstract

Candidiasis is one of the most common fungal diseases that can pose a threat to life in immunodeficient individuals, particularly in its disseminated form. Not only fungal invasion but also fatal infection-related inflammation are common causes of systemic candidiasis. In this study, we investigated in vitro immunomodulatory properties of the antifungal pea defensin Psd1 upon Candida albicans infection. Using the real-time PCR, we showed that Psd1 inhibited the antimicrobial peptide HBD-2 and pro-inflammatory cytokines IL-1 and IL-8 downregulation at mRNA level in epithelium cells caused by C. albicans infection. By using the Caco-2/immune cells co-culture upon C. albicans infection and the multiplex xMAP assay, we demonstrated that this pathogenic fungus induced a pronounced host defense response; however, the cytokine responses were different in the presence of dendritic cells or monocytes. We revealed that Psd1 at a low concentration (2 µM) had a pronounced immunomodulatory effect on the Caco-2/immune cells co-culture upon fungal infection. Thus, we hypothesized that the pea defensin Psd1 might be an effective agent in the treatment of candidiasis not only due to its antifungal activity, but also owing to its ability to modulate a protective immune response upon infection.

A Review of Bioactive Compound Effects from Primary Legume Protein Sources in Human and Animal Health

“…Immunomodulatory BPs interact with the immune system and can improve its ability to fight off infection by supporting adaptive immune responses through the targeting and upregulating of agents within the body, such as natural killer cells, lymphocytes, and macrophages. The defensin peptide Psd1 in pea has been shown to activate immune cells and increase the immune response of human immune cells [50]. Soymetide-13, a BP from soybean, has been shown to stimulate phagocytosis, which allows the body's immune cells to identify and intercept potential pathogens in the body [51].…”

Antifungal Plant Defensins as an Alternative Tool to Combat Candidiasis

“…Psd1 is able to pass through the Caco-2 cell monolayer Trans-epithelial transport assay, using FITC-labelled Psd1 [79] Insignificant changes in cytokine profiles; increase in the production of IL-6, IL-8/CXCL8, and IP-10; induction of expression of genes coding IL-1β, IL-8/CXCL8, and HBD2 It has been shown that plant defensins have immunomodulatory, mainly pro-inflammatory, effects on epithelial cells, which are the first line of defense against pathogens (Table 3). Psd1 upregulates the expression of gene coding human β-defensin-2 (HBD2), IL-1β, and IL-8/CXCL8, as well as increases the production of IL-6 and IP-10 in intestinallike epithelial cells Caco-2 [79]. γ-Thionin upregulates the expression of gene coding membrane receptor TLR2 and cytokines (TNFα, IL-1β, and IL-10), activates the transcriptional factors of inflammatory response (E2F-1, EGR, CBF, AP-1, and others), and increases NO production in bovine mammary epithelial cells (bMECs) [107,108].…”

“…The immunomodulatory effects of plant defensins on epithelial cells also persist under infection. Thus, the immunomodulatory effects of Psd1 on Caco-2 cells and γ-thionin on bMECs infected by C. albicans or S. aureus , respectively, are generally the same as those without infection [ 79 , 107 , 108 ]. It is worth mentioning that γ-thionin significantly inhibits S. aureus internalization into bMECs.…”

“…Ppdef1 from P. pentandra rapidly and efficiently penetrates human nail plates consisting of keratinized epidermal cells, making it an excellent candidate for a novel topical treatment of onychomycosis [ 66 ]. At the same time, Psd1 is able to pass through a Caco-2-cell monolayer simulating intestinal epithelium, which makes its further interaction with immune and endothelial cells possible [ 79 ].…”

“…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 ].…”