STAT1-L351F is associated with enhanced interferon signaling and susceptibility to Talaromyces marneffei infection

Dysregulated STAT1 signaling is associated with increased susceptibility to fungal infections, but its transcriptomic impact during Talaromyces marneffei infection remains poorly understood. Bulk lung transcriptomic profiling was performed to compare gene expression differences between wild-type (WT) and Stat1-L351F knock-in mice during Talaromyces marneffei infection. Lung tissues were harvested from female mice at 16 days post-infection (dpi). Total RNA was extracted using TRIzol reagent (Invitrogen). RNA sequencing libraries were constructed using the NEBNext Ultra II RNA Library Prep Kit and sequenced on an Illumina NovaSeq 6000 platform to generate paired-end clean reads. Reads were aligned to the mouse reference genome (GRCm38/mm10) using HISAT2. Differential gene expression analysis was conducted using the DESeq2 package in R, with genes showing an adjusted P value < 0.05 defined as differentially expressed. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and preranked Gene Set Enrichment Analysis (GSEA) were performed using the clusterProfiler package in R to characterize inflammatory, antimicrobial, and interferon-related biological processes.