Abstract
Brucellosis, a zoonotic disease caused by Brucella infection, poses a major threat to both global health and livestock productivity. Although reproductive impairment is well established, the molecular mechanisms driving testicular immunopathology remain poorly understood. In this study, single-cell RNA sequencing was used to delineate transcriptional changes in goat testicular tissues under physiological and Brucella-infected conditions, revealing dynamic immunological remodeling of the testicular microenvironment. Infection induced marked shifts in T cell and macrophage phenotypes, with T cells exhibiting pronounced hyperactivation linked to CD45-mediated signaling cascades. Thioredoxin-interacting protein ( TXNIP), a gene strongly up-regulated in response to infection, emerged as a potential immunotherapeutic target. Intercellular communication networks were significantly disrupted in infected testes, with CD39- and JAM-dependent signaling pathways implicated in the erosion of immune privilege. Regulon analysis further identified GATA3, IRF5, SEMA4A, and HCLS1 as transcriptional regulators associated with T cells and macrophages in infected testes. These findings provide novel insights into the molecular mechanisms driving testicular immunopathology during Brucella infection and highlight candidate targets for immunomodulatory intervention in disease control and livestock reproductive health.