Immune genes CD247 STAT1 and LCK mediate host–pathogen interactions in sporotrichosis

Sporotrichosis is a chronic subcutaneous infection caused by the Sporothrix complex, a dimorphic fungus that exhibits significant clinical heterogeneity. However, the molecular targets and underlying mechanisms of Sporothrix globosa infection remain unclear. Therefore, in this study, we aimed to integrate whole-transcriptome sequencing analysis of skin lesion tissues from patients with sporotrichosis and healthy controls. In addition, differential gene expression screening, protein-protein interaction network construction, and functional enrichment analysis. We systematically identified the key immune-related genes, Cluster of Differentiation 247 (CD247), Signal Transducer and Activator of Transcription 1 (STAT1), and Lymphocyte-Specific Tyrosine Kinase (LCK), which are majorly upregulated during infections. The high expression of these genes in the disease group was consistently validated by western blot, quantitative polymerase chain reaction, and immunohistochemistry. Mechanistic analysis revealed the contribution of these genes to sporotrichosis-dysregulated immune response. This occurs by causing excessive activation of the interferon signaling pathway, lymphocyte overactivation, and the JAK-STAT signaling pathway, which leads to the host immune imbalance. This suggests their central role in immune evasion and overactivation during sporotrichosis. In this novel study, we revealed the pathological regulatory role of the CD247-STAT1-LCK molecular network in sporotrichosis, which provided novel insights into fungal-host interactions and identified potential therapeutic targets for immune-modulating antifungal treatments.