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Comprehensive analysis of human keratinocyte interactions with Candida albicans and Candida parapsilosis

Novák, Ádám and Zajta, Erik and Csikós, Máté Lajos and Halmos, Emese and Horváth, Márton and Tildy, Orsolya and Szekeres, András and Svorenj, Gergő and Gémes, Nikolett and Szebeni, Gábor and Tóth, Renáta and Gácser, Attila (2025) Comprehensive analysis of human keratinocyte interactions with Candida albicans and Candida parapsilosis. VIRULENCE, 16 (1). No. 2532815. ISSN 2150-5594

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Abstract

In recent years, microbiome studies have revealed that Candida species are common colonizers of the human skin. The distribution of species, however, varies greatly. Although C. parapsilosis is more likely to resemble skin commensals, opinions are divided, and discrepancies are present regarding C. albicans that is also often associated with cutaneous candidiasis. Therefore, we aimed to thoroughly assess the nature of skin epithelial cell - Candida interactions. To study speciesspecific host responses, we examined internalization, cytokine and metabolic responses in different keratinocytes (HaCaT, HPV-KER) along with host cell damage following fungal stimuli. To rigorously examine yeast-keratinocyte interactions, we applied two distinct isolates of both C. albicans (SC5314, WO-1) and C. parapsilosis (GA1, CLIB214). Comparison of the two fungi’s virulence revealed that while C. albicans effectively adheres to human keratinocytes and causes subsequent damage, C. parapsilosis is unable to establish lasting physical contact and causes less harm. In terms of keratinocyte response, both cell lines showed significantly enhanced cellular (internalization), humoral (IL-6, IL-8) and metabolic responses (2-ketoglutaric acid, citric acid, threorine, hypotaurine) to C. albicans strains, while those towards C. parapsilosis remained relatively low or similar to the control condition. Under certain conditions strain preference was also detected. Of the two cell lines, HPV-KER was more sensitive, as besides interspecies differences, intraspecies differences were also measurable. These results suggest that C. albicans triggers an enhanced antifungal response, thus does not closely resemble skin commensals, like C. parapsilosis. Furthermore, HPV-KER might serve as a more applicable tool for studying keratinocyte antifungal responses.

Item Type: Article
Additional Information: Funding Agency and Grant Number: EU's Horizon 2020 research and innovation program [739593]; HUN-REN [2001007]; Hungarian Scientific Research Fund NKFIH [K147510]; Centre of Excellence for Interdisciplinary Research, Development and Innovation of the University of Szeged, Competence Centre for Molecular Biology, Bionics and Biotechnology; Louis-Jeantet Foundation; Hungarian Academy of Sciences [BO/00351/23/8, BO/00582/22/8]; National Research, Development and Innovation Office (NKFIH) [PD 138450]; National Research, Development, and Innovation Office; National Academy of Scientist Education Program of the National Biomedical Foundation; [2023-1.1.1-PIACI_FKUSZ-2024-00036]; [FK22-142877] Funding text: The project was supported by EU's Horizon 2020 research and innovation program under grant agreement No. [739593], by the grant HUN-REN [2001007], by the Hungarian Scientific Research Fund NKFIH [K147510] and the Centre of Excellence for Interdisciplinary Research, Development and Innovation of the University of Szeged, Competence Centre for Molecular Biology, Bionics and Biotechnology. The research was also supported by the Louis-Jeantet Foundation. RT was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences, BO/00351/23/8. R.T.was financed by the National Research, Development and Innovation Office (NKFIH) through grant no. [PD 138450]. This research was funded by the 2023-1.1.1-PIACI_F & Oacute;KUSZ-2024-00036 (NKFIH), [FK22-142877] (GS), grant from the National Research, Development, and Innovation Office. This work was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences BO/00582/22/8 (GS). This research work and G.S. was supported by the National Academy of Scientist Education Program of the National Biomedical Foundation under the sponsorship of the Hungarian Ministry of Culture and Innovation.
Uncontrolled Keywords: Keratinocyte; candida; interaction; pathogenic fungi; immune response
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 02 Sep 2025 15:24
Last Modified: 02 Sep 2025 15:24
URI: https://real.mtak.hu/id/eprint/223218

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