Brucella Dysregulates Monocytes and Inhibits Macrophage Polarization through LC3-Dependent Autophagy

Abstract

Brucellosis is caused by infection with <i>Brucella</i> species and exhibits diverse clinical manifestations in infected humans. Monocytes and macrophages are not only the first line of defense against <i>Brucella</i> infection but also a main reservoir for <i>Brucella</i>. In the present study, we examined the effects of <i>Brucella</i> infection on human peripheral monocytes and monocyte-derived polarized macrophages. We showed that <i>Brucella</i> infection led to an increase in the proportion of CD14⁺⁺CD16^- monocytes and the expression of the autophagy-related protein LC3B, and the effects of <i>Brucella</i>-induced monocytes are inhibited after 6 weeks of antibiotic treatment. Additionally, the production of IL-1β, IL-6, IL-10, and TNF-α from monocytes in patients with brucellosis was suppressed through the LC3-dependent autophagy pathway during <i>Brucella</i> infection. Moreover, <i>Brucella</i> infection inhibited macrophage polarization. Consistently, the addition of 3-MA, an inhibitor of LC3-related autophagy, partially restored macrophage polarization. Intriguingly, we also found that the upregulation of LC3B expression by rapamycin and heat-killed <i>Brucella in vitro</i> inhibits M2 macrophage polarization, which can be reversed partially by 3-MA. Taken together, these findings reveal that <i>Brucella</i> dysregulates monocyte and macrophage polarization through LC3-dependent autophagy. Thus, targeting this pathway may lead to the development of new therapeutics against Brucellosis.