Recognition of Brucella abortus drives M2 like polarization and impaired antigen presentation in monocyte derived macrophages.

Macrophages play essential roles in host defense and the resolution of tissue damage. Under inflammatory conditions, circulating monocytes migrate from the bloodstream to affected tissues, where they differentiate into macrophages whose characteristics are shaped by the local microenvironment. Brucellosis, a zoonotic disease caused by Brucella spp., is characterized by the ability of these pathogens to invade and persist primarily within monocytes and macrophages. Although Brucella spp. can activate these cells, it remains unclear whether Brucella-host interactions modulate monocyte-to-macrophage differentiation. The aim of this work was to examine how Brucella abortus recognition influences macrophage differentiation. Monocytes were differentiated into macrophages with M-CSF in the presence of B. abortus, followed by phenotypic and functional characterization. The macrophages differentiated in the presence of B. abortus presented reduced expression of antigen-presenting markers (HLA-DR, HLA-ABC and CD86), increased M2/pro-regenerative features, and increased basal secretion of cytokines and phagocytic activity. However, they fail to respond to further stimulation (e.g., E. coli LPS) and exhibit poor T cell priming capacity. Macrophages differentiated in the presence of B. abortus exhibit a mixed profile characterized by a reduction in antigen-presenting molecules, which impairs the adaptive immune response, while adopting an M2-like/pro-regenerative phenotype contributes to chronic infection. Moreover, macrophages differentiated in the presence of B. abortus secrete cytokines and chemokines, perpetuating inflammation at the infection site, a hallmark of brucellosis.