Identification of potential targets in bone destruction by Talaromyces marneffei: Insights from data-independent acquisition proteomics

To investigate the molecular mechanisms of Talaromyces marneffei (TM)-induced bone destruction through proteomic analysis using Data-Independent Acquisition (DIA) technology. Bone tissue samples were collected from eight patients (four TM-infected cases, four non-infectious controls). Samples underwent histopathological evaluation (Hematoxylin and Eosin Staining and Wright-Giemsa staining), DIA proteomics analysis, and protein validation through immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Comparative analysis between Control (Con) and Infected (Inf) groups showed similar demographics but significantly elevated inflammatory markers in Inf. Histopathology revealed extensive bone destruction, marked inflammatory infiltration, fibrinoid necrosis, and altered hematopoietic cell populations in Inf specimens compared to Con. DIA proteomics identified 5930 quantifiable proteins, with 509 differentially expressed proteins (DEPs) between groups. Gene ontology and Kyoto encyclopedia of genes and genomes pathway analyses revealed significant enrichment of inflammation and immune response-related functions in Inf. COMMD1 was significantly downregulated while IL-17 was upregulated in Inf, as validated by immunohistochemistry and ELISA. DIA proteomics identified downregulated COMMD1 and upregulated IL-17 in TM-induced bone destruction, suggesting potential diagnostic biomarkers and therapeutic targets through inflammatory pathway modulation.