Single-cell transcriptomics reveals dynamic reprogramming of testicular immunity in Brucella-infected goat testis

Brucellosis, a zoonotic disease caused by Brucella infection, significantly threatens global health and livestock productivity. While its effects on reproductive organs are recognized, the mechanisms driving testicular immunopathology remain poorly understood. Here, we employed single-cell RNA sequencing to systematically compare the transcriptional landscapes of normal and Brucella-infected goat testicular tissues, revealing dynamic remodeling of the testicular immune microenvironment. Our analysis identified significant alterations in T cell and macrophage states following infection, with T cells exhibiting pronounced activation linked to CD45 signaling pathway activity. We further pinpointed key differentially expressed genes, including TXNIP (thioredoxin-interacting protein), a potential therapeutic target implicated in anti-Brucella. Cell-cell communication analysis highlighted disrupted intercellular networks in infected testes, particularly emphasizing the critical roles of CD39 and JAM signaling pathways in modulating immune privilege. Additionally, GATA3, IRF5, SEMA4A and HCLS1 were identified as the most significant regulons associated with T cells and macrophages during the Brucella infected. These findings provide novel insights into the molecular mechanisms driving testicular immunopathology during Brucella infection and offer potential targets for intervention strategies in disease control and livestock breeding.