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

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 species-specific 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.