Year: 2025
Type: article
Abstract: Description People with chronic hyperglycemia are more susceptible to Candida albicans skin infections, yet the mechanisms underpinning their poor clinical outcomes compared to euglycemic individuals remain elusive. Using in vivo and in vitro systems, we examined how hyperglycemia impacts skin antifungal defenses. Mice were rendered hyperglycemic by injecting streptozotocin and infected s.c. with C. albicans. Hyperglycemic mice exhibited greater susceptibility, with larger lesions and higher fungal burden. Histological analysis revealed larger abscesses, more abundant hyphae, and impaired control of fungal invasion. However, pro-inflammatory cytokine and chemokine levels remained unchanged between groups. Hyperglycemia upregulated gene expression of pathogen recognition receptors (Clec7a and Tlr4) and TLR adaptor proteins Trif and Tirap in infected tissues. In vitro, RNAseq analysis from mouse dermal macrophages cultured in high glucose and infected with C. albicans showed enrichment of genes involved in antimicrobial effectors and C-type lectin receptor pathway. When we determined the effect of high glucose in C. albicans ingestion, we observed impaired phagocytic activity in both dermal macrophages and human keratinocytes. This impairment was reversed by the DR1 antagonist Laminarin. These findings implicate a heretofore unknown negative role of DR1 in hyperglycemia-induced phagocytic dysfunction, contributing to impaired fungal control in hyperglycemia. Funding Sources Supported by: 1T32AI112541-01A1 (DR) and 1R01AI180777-01A1 (CHS) Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)
Source: The Journal of Immunology
Institutions: Vanderbilt University Medical Center, Vanderbilt University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4416451233
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