Brucella-infected macrophage-derived microparticles enhance the host anti-Brucella acquired immune response.

Microparticles (MPs) serve as critical mediators of intercellular communication by shuttling bioactive molecules, holding significant potential for clinical diagnostics and next-generation vaccine development. Brucella, an intracellular pathogen responsible for severe zoonosis, evades host immunity through persistent infection; however, the role of Brucella-induced MPs in modulating adaptive immunity remains poorly defined. In this study, we demonstrate that the infection of RAW264.7 macrophages with the attenuated Brucella melitensis strain M5 triggers robust MP release. These MPs enhance host defense by promoting bacterial clearance and restricting intracellular survival. In murine models, MPs elicit potent Th1-polarized immunity, characterized by elevated IgG2a titers and increased IFN-γ production. Mechanistically, MPs derived from M5-infected macrophages activate the nuclear factor-κB (NF-κB) pathway in bone marrow-derived dendritic cells (BMDCs), augmenting the secretion of IL-12 and TNF-α. Critically, MPs prime cytotoxic T lymphocytes (CTLs) through both direct and indirect pathways, resulting in the specific lysis of Brucella-infected targets. Collectively, Brucella-induced MPs function as integrated immunogenic units that bridge innate recognition with adaptive effector responses, unveiling a novel host-pathogen interaction axis and advancing MPs-based strategies against brucellosis.