β-Glucan–mediated macrophage priming enhances macrophage activation and host defense against Mycobacterium tuberculosis infection

Tuberculosis remains a major cause of infectious mortality worldwide, highlighting the need for complementary therapeutic strategies beyond conventional antibiotics. Host-directed approaches may enhance macrophage-mediated control of infection. In this study, we investigated the effects of β-glucan priming combined with drug-loaded yeast-derived β-glucan particles (DYDGP) in an in vitro macrophage model of Mycobacterium tuberculosis infection. Phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 macrophages were compared across unprimed, β-glucan-only, antibiotic-only, and β-glucan-primed/DYDGP-treated groups. β-Glucan priming combined with DYDGP treatment was associated with enhanced receptor-mediated phagocytic activity, improved intracellular bacterial control, and preserved macrophage integrity. These effects were associated with increased intracellular reactive oxygen species (ROS) production, enhanced phagolysosomal maturation, and altered autophagic activity. Colony-forming unit (CFU) analysis showed that β-glucan-primed macrophages treated with DYDGP exhibited a significantly lower bacterial burden than the unprimed, β-glucan-only, and antibiotic-only groups at 1, 6, and 24 h post-infection. Unprimed macrophages showed progressive bacterial growth, with log CFU values of 4.2, 4.8, and 5.2, whereas β-glucan-primed/DYDGP-treated macrophages showed reduced values of 3.3, 2.5, and 2.1, respectively. β-Glucan-only treatment resulted in log CFU values of 4.2, 4.4, and 4.7, while antibiotic-only treatment resulted in values of 4.2, 4.1, and 3.9 at the corresponding time points. These findings suggest that β-glucan priming combined with DYDGP treatment may enhance intracellular control of M. tuberculosis in this macrophage model and support further investigation of this approach as a potential adjunctive strategy for tuberculosis.