Influence of fungi on epithelial homeostasis and role in inflammatory diseases

SUMMARYThe skin harbors a diverse fungal community that contributes to both epidermal homeostasis and inflammatory disease. Historically, studies of cutaneous fungi focused primarily on opportunistic infections in immunocompromised hosts. Advances in sequencing technologies and metagenomic analyses have revealed that commensal yeasts of the skin microbiome likely influence host physiology and cutaneous disease severity. In this review, we summarize the current knowledge of host-fungal interactions at the skin epithelium, with particular emphasis on the yeast genera Malassezia and Candida. We discuss how fungal colonization shapes epidermal biology through direct interactions with keratinocytes and immune cells, highlighting fungal virulence factors such as secreted proteases and candidalysin, as well as host-sensing pathways. We further examine how these interactions contribute to inflammatory skin diseases, particularly atopic dermatitis and psoriasis, and how fungi participate in polymicrobial networks with bacteria and viruses to alter susceptibility to infection. Finally, we discuss how emerging therapeutic strategies change the fungal composition on skin. These advances suggest the importance of fungi as active regulators of skin immunity and emphasize key knowledge gaps that need to be addressed in future studies to better understand how they contribute to cutaneous diseases.