<![CDATA[Cutaneous Candida albicans infection is characterized by persistent inflammation, epidermal damage, and dysregulated immune responses. Silver nanoparticles (AgNPs) have emerged as promising antifungal agents with additional immunomodulatory properties; however, their effects on skin pathology and local immune responses during candidiasis remain incompletely defined. This study aimed to investigate the therapeutic effects of a topical AgNP-based cream in a murine model of C. albicans–induced skin infection. AgNPs were green-synthesized using an aqueous leaf extract of Piper ornatum. A murine model of cutaneous C. albicans infection was established, and infected mice were treated topically with AgNP-based cream formulations at concentrations of 4% or 6%. Disease severity was assessed through macroscopic skin evaluation and histopathological analysis. Immune modulation was examined by flow cytometric analysis of CD4⁺ T-cell subsets expressing TNFα and IL-17, as well as CD11b⁺ myeloid cells expressing IL-6 and IL-10. Untreated infected mice exhibited severe cutaneous pathology, including persistent erythema, erosive lesions, epidermal hyperkeratosis, and acanthosis. These changes were accompanied by marked immune dysregulation, characterized by expansion of CD4⁺IL-17⁺ T-cells, suppression of TNFα-producing CD4⁺ T-cells, increased IL-6 expression, and reduced IL-10 production in CD11b⁺ myeloid cells. Topical AgNP treatment significantly ameliorated macroscopic and histological skin damage, restoring epidermal architecture toward normal. Immunologically, AgNP therapy attenuated pathological Th17 responses, reduced IL-6-producing myeloid cells, enhanced IL-10 expression, and maintained TNFα at controlled levels. Both AgNP concentrations were effective, with the 4% AgNP formulation showing slightly superior normalization of epidermal thickness and inflammatory markers. Overall, topical AgNP-based cream effectively alleviated cutaneous C. albicans infection by combining antifungal activity with coordinated immunomodulation of both adaptive and innate immune responses. By suppressing excessive IL-17– and IL-6–driven inflammation while promoting regulatory immune pathways, AgNP treatment supports tissue repair and immune homeostasis, highlighting its potential as a therapeutic strategy for cutaneous candidiasis.]]>
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