Candida spp diminish viral susceptibility of human keratinocytes and promote an antiviral state
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Presented at: Society for Investigative Dermatology 2025
Date: 2025-05-07 00:00:00
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Summary: Abstract Body: We have shown that S. aureus enhances viral susceptibility of keratinocytes (KC). However, little is known about the effect of fungi on KC viral susceptibility. We found that exposure of KC to Candida (C.) albicans (104 colony forming units [CFU]) or C. parapsilosis (103 CFU) diminished viral susceptibility, whereas Saccharomyces cerevisiae or Malassezia sympodialis exposure had little or no effect, respectively. To extend these findings to additional Candida species (spp) we observed that KC exposed to either C. tropicalis (102 CFU) or C. glabrata (104 CFU) reduced vaccina virus (VV)-induced cytopathic effect (65±18% decrease, p=0.066; 32±14% decrease, p<0.05, respectively). Collectively, these findings suggest that Candida spp diminish KC viral susceptibility. To understand the molecular changes occurring in Candida-exposed KC that would promote an antiviral response, we quantified gene transcripts associated with antiviral activity from KC following C. parapsilosis or C. albicans exposure (104 CFU). We observed an increase in genes related to the inflammasome (NLRP3, 6.2±0.8 fold-increase, p<0.05; IL1B, 21.6±2.1 fold-increase, p<0.0001), antimicrobial peptides (RNASE7, 6.2±2.6 fold-increase, p=0.051; DEFB3, 102.3±73.4 fold-increase, p<0.05) and type 1 interferons (IFNA1, 2.1±0.4 fold-increase, p<0.05; IFNB, 1.5±0.1 fold-increase, p<0.05). Only two genes were significantly upregulated following C. albicans exposure: IL1B (11.9±2.2 fold-increase, p<0.01) and RNASE7 (3.37±0.9 fold-increase, p<0.05). When KC exposed to C. parapsilosis (104 CFU), but not C. albicans, were infected with VV for 6 hours, NLRP3 (2.77±1.7 fold-increase), DEFB3 (29.9±15.9 fold-increase), and RNASE7 (3.80±0.8 fold-increase) transcripts remained at higher levels compared to unexposed KC. This research suggests that the composition of the cutaneous microbiome (e.g. presence of specific Candida spp) can dictate human skin viral susceptiblity. Liam F. Peterson<sup>1</sup>, Lisa Beck<sup>2, 1</sup>, Matthew G. Brewer<sup>2</sup> 1. Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, United States. 2. Dermatology, University of Rochester Medical Center, Rochester, NY, United States. Innate Immunity, Microbiology, and Microbiome