{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T18:38:14Z","timestamp":1782931094968,"version":"3.54.5"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T00:00:00Z","timestamp":1682208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Science Foundation","award":["22-25-00654"],"award-info":[{"award-number":["22-25-00654"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u00b5M) 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.<\/jats:p>","DOI":"10.3390\/ijms24097712","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T04:01:23Z","timestamp":1682308883000},"page":"7712","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Immunomodulatory Effects of the Pea Defensin Psd1 in the Caco-2\/Immune Cells Co-Culture upon Candida\u00a0albicans Infection"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8887-2898","authenticated-orcid":false,"given":"Ivan V.","family":"Bogdanov","sequence":"first","affiliation":[{"name":"M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serafima I.","family":"Fateeva","sequence":"additional","affiliation":[{"name":"M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6431-811X","authenticated-orcid":false,"given":"Alexander D.","family":"Voropaev","sequence":"additional","affiliation":[{"name":"G.N. Gabrichevsky Research Institute for Epidemiology and Microbiology, Admiral Makarov St. 10, 125212 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5950-249X","authenticated-orcid":false,"given":"Tatiana V.","family":"Ovchinnikova","sequence":"additional","affiliation":[{"name":"M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina I.","family":"Finkina","sequence":"additional","affiliation":[{"name":"M.M. Shemyakin & Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2154548-14","DOI":"10.1080\/19490976.2022.2154548","article-title":"From Intestinal Colonization to Systemic Infections: Candida albicans Translocation and Dissemination","volume":"14","author":"Sprague","year":"2022","journal-title":"Gut Microbes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"104477","DOI":"10.1016\/j.micpath.2020.104477","article-title":"Are Candida albicans isolates from the oral cavity of HIV-infected patients more virulent than from non-HIV-infected patients? Systematic review and meta-analysis","volume":"149","author":"Orlandini","year":"2020","journal-title":"Microb. Pathog."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.micres.2017.02.002","article-title":"Candida albicans Infection and Intestinal Immunity","volume":"198","author":"Tong","year":"2017","journal-title":"Microbiol. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nrmicro2636","article-title":"Growth of Candida albicans Hyphae","volume":"9","author":"Sudbery","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/978-3-030-67452-6_11","article-title":"Candida Pathogenicity and Interplay with the Immune System","volume":"1313","author":"Valand","year":"2021","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1080\/21505594.2015.1004977","article-title":"Adaptive Immune Responses to Candida albicans Infection","volume":"6","author":"Richardson","year":"2015","journal-title":"Virulence"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s40104-022-00796-y","article-title":"The Dual Antimicrobial and Immunomodulatory Roles of Host Defense Peptides and Their Applications in Animal Production","volume":"13","author":"Wu","year":"2022","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.3389\/fmicb.2018.01612","article-title":"Immunomodulation as Therapy for Fungal Infection: Are We Closer?","volume":"9","author":"Sam","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Perez-Rodriguez, A., Eraso, E., Quind\u00f3s, G., and Mateo, E. (2022). Antimicrobial Peptides with Anti-Candida Activity. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169264"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.semcdb.2018.02.023","article-title":"Multifaceted Immune Functions of Human Defensins and Underlying Mechanisms","volume":"88","author":"Fruitwala","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.peptides.2016.02.008","article-title":"Defensin \u03b3-thionin from Capsicum chinense Has Immunomodulatory Effects on Bovine Mammary Epithelial Cells during Staphylococcus aureus Internalization","volume":"78","year":"2016","journal-title":"Peptides"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1021\/acsptsci.0c00035","article-title":"Modulation of Lymphocyte Potassium Channel KV1.3 by Membrane-penetrating, Joint-targeting Immunomodulatory Plant Defensin","volume":"3","author":"Ong","year":"2020","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Finkina, E.I., Bogdanov, I.V., Ignatova, A.A., Kanushkina, M.D., Egorova, E.A., Voropaev, A.D., Stukacheva, E.A., and Ovchinnikova, T.V. (2022). Antifungal Activity, Structural Stability, and Immunomodulatory Effects on Human Immune Cells of Defensin from the Lentil Lens culinaris. Membranes, 12.","DOI":"10.3390\/membranes12090855"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3389\/fcimb.2017.00249","article-title":"Psd1 Effects on Candida albicans Planktonic Cells and Biofilms","volume":"7","author":"Silva","year":"2017","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/bip.22570","article-title":"Psd1 binding affinity toward fungal membrane components as assessed by SPR: The role of glucosylceramide in fungal recognition and entry","volume":"102","author":"Domitrovic","year":"2014","journal-title":"Biopolymers"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.bbamem.2012.02.012","article-title":"Evaluation of the Membrane Lipid Selectivity of the Pea Defensin Psd1","volume":"1818","author":"Teixeira","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Amaral, V.S.G.D., Santos, S.A.C.S., de Andrade, P.C., Nowatzki, J., J\u00fanior, N.S., de Medeiros, L.N., Gitirana, L.B., Pascutti, P.G., Almeida, V.H., and Monteiro, R.Q. (2020). Pisum sativum Defensin 1 Eradicates Mouse Metastatic Lung Nodules from B16F10 Melanoma Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082662"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Verhoeckx, K., Cotter, P., L\u00f3pez-Exp\u00f3sito, I., Kleiveland, C., Lea, T., Mackie, A., Requena, T., Swiatecka, D., and Wichers, H. (2015). The Impact of Food Bioactives on Health: In Vitro and Ex Vivo Models, Springer.","DOI":"10.1007\/978-3-319-16104-4"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"781","DOI":"10.3389\/fphar.2017.00781","article-title":"Experimental Evaluation of the Transport Mechanisms of PoIFN-\u03b1 in Caco-2 Cells","volume":"8","author":"Liu","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/978-1-61779-191-8_9","article-title":"Optimization of the Caco-2 Permeability Assay to Screen Drug Compounds for Intestinal Absorption and Efflux","volume":"763","author":"Press","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"538","DOI":"10.3109\/00498254.2011.643256","article-title":"The Impact of P-glycoprotein Mediated Efflux on Absorption of 11 Sedating and Less-sedating Antihistamines Using Caco-2 Monolayers","volume":"42","author":"Crowe","year":"2012","journal-title":"Xenobiotica"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1093\/infdis\/jit413","article-title":"Inflammatory Monocytes Mediate Early and Organ-Specific Innate Defense During Systemic Candidiasis","volume":"209","author":"Ngo","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"235","DOI":"10.2174\/1389201003378924","article-title":"Cytokines in Candidiasis and Apergillosis","volume":"1","author":"Mencacci","year":"2000","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mengesha, B.G., and Conti, H.R. (2017). The Role of IL-17 in Protection against Mucosal Candida Infections. J. Fungi, 3.","DOI":"10.3390\/jof3040052"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"154882","DOI":"10.1016\/j.cyto.2019.154882","article-title":"Candida albicans SC5314 Inhibits NLRP3\/NLRP6 Inflammasome Expression and Dampens Human Intestinal Barrier Activity in Caco-2 Cell Monolayer Model","volume":"126","author":"Mao","year":"2020","journal-title":"Cytokine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1086\/315250","article-title":"Stimulation of Macrophage Inflammatory Protein-1alpha, Macrophage Inflammatory Protein-1beta, and RANTES by Candida albicans and Cryptococcus neoformans in Peripheral Blood Mononuclear Cells from Persons with and without Human Immunodeficiency Virus Infection","volume":"181","author":"Huang","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/j.1469-0691.2011.03676.x","article-title":"Adjunctive Immunotherapy with Recombinant Cytokines for the Treatment of Disseminated Candidiasis","volume":"18","author":"Kullberg","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"208","DOI":"10.4049\/jimmunol.1501204","article-title":"IL-27 Induced by Select Candida spp. via TLR7\/NOD2 Signaling and IFN-\u03b2 Production Inhibits Fungal Clearance","volume":"197","author":"Patin","year":"2016","journal-title":"J. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jim.2008.09.021","article-title":"MIG (CXCL9) is a more Sensitive Measure than IFN-gamma of Vaccine Induced T-cell Responses in Volunteers Receiving Investigated Malaria Vaccines","volume":"340","author":"Berthoud","year":"2009","journal-title":"J. Immunol. Methods"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/mi.2010.22","article-title":"IL-22 Defines a Novel Immune Pathway of Antifungal Resistance","volume":"3","author":"Zelante","year":"2010","journal-title":"Mucosal Immunol."},{"key":"ref_31","unstructured":"(2020, April 22). EUCAST Definitive Document, E.DEF 7.3.2: Method for the Determination of Broth Dilution Minimum Inhibitory Concentrations of Antifungal Agents for Yeasts. Available online: https:\/\/www.eucast.org\/astoffungi\/methodsinantifungalsusceptibilitytesting\/susceptibility_testing_of_yeasts\/."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7.6.1","DOI":"10.1002\/0471142735.im0706s16","article-title":"Isolation of Monocyte\/Macrophage Populations","volume":"16","author":"Wahl","year":"1995","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/0471142735.im0732s99","article-title":"Isolation and Generation of Human Dendritic cells","volume":"99","author":"Nair","year":"2012","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5949","DOI":"10.1128\/JVI.75.13.5949-5957.2001","article-title":"Human cytomegalovirus chemokine receptor gene US28 is transcribed in latently infected THP-1 monocytes","volume":"75","author":"Beisser","year":"2001","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"766","DOI":"10.3346\/jkms.2010.25.5.766","article-title":"Changes of antimicrobial peptides and transepidermal water loss after topical application of tacrolimus and ceramide-dominant emollient in patients with atopic dermatitis","volume":"25","author":"Park","year":"2010","journal-title":"J. Korean Med. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.ejpb.2008.03.008","article-title":"Validation of reference genes for qPCR studies on Caco-2 cell differentiation","volume":"69","author":"Piana","year":"2008","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Untergasser, A., Ruijter, J.M., Benes, V., and van den Hoff, M.J.B. (2021). Web-based LinRegPCR: Application for the Visualization and Analysis of (RT)-qPCR Amplification and Melting Data. BMC Bioinform., 22.","DOI":"10.1186\/s12859-021-04306-1"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/7712\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:21:32Z","timestamp":1760124092000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/7712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,23]]},"references-count":37,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ijms24097712"],"URL":"https:\/\/doi.org\/10.3390\/ijms24097712","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,23]]}}}