Comprehensive analysis of human keratinocyte interactions with <i>Candida albicans</i> and <i>Candida parapsilosis</i>

In recent years, microbiome studies have revealed that <i>Candida</i> species are common colonizers of the human skin. The distribution of species, however, varies greatly. Although <i>C. parapsilosis</i> is more likely to resemble skin commensals, opinions are divided, and discrepancies are present regarding <i>C. albicans</i> that is also often associated with cutaneous candidiasis. Therefore, we aimed to thoroughly assess the nature of skin epithelial cell - <i>Candida</i> 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 <i>C. albicans</i> (SC5314, WO-1) and <i>C. parapsilosis</i> (GA1, CLIB214). Comparison of the two fungi’s virulence revealed that while <i>C. albicans</i> effectively adheres to human keratinocytes and causes subsequent damage, <i>C. parapsilosis</i> 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 <i>C. albicans</i> strains, while those towards <i>C. parapsilosis</i> 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 <i>C. albicans</i> triggers an enhanced antifungal response, thus does not closely resemble skin commensals, like <i>C. parapsilosis</i>. Furthermore, HPV-KER might serve as a more applicable tool for studying keratinocyte antifungal responses.