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

Abstract

Brucellosis is caused by infection with Brucella species and exhibits diverse clinical manifestations in infected humans. Monocytes and macrophages are not only the first line of defense against Brucella infection but also a main reservoir for Brucella. In the present study, we examined the effects of Brucella infection on human peripheral monocytes and monocyte-derived polarized macrophages. We showed that Brucella 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 Brucella-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 Brucella infection. Moreover, Brucella 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 Brucella in vitro inhibits M2 macrophage polarization, which can be reversed partially by 3-MA. Taken together, these findings reveal that Brucella dysregulates monocyte and macrophage polarization through LC3-dependent autophagy. Thus, targeting this pathway may lead to the development of new therapeutics against Brucellosis.

Biochanin a Enhances the Defense Against Salmonella enterica Infection Through AMPK/ULK1/mTOR-Mediated Autophagy and Extracellular Traps and Reversing SPI-1-Dependent Macrophage (MΦ) M2 Polarization

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An Autoimmune Disease-Associated Risk Variant in the TNFAIP3 Gene Plays a Protective Role in Brucellosis That Is Mediated by the NF-κB Signaling Pathway

“…CD14 + monocytes were cultured in the presence of 1.0 μg/ml smooth lipopolysaccharides (S-LPS) from Escherichia coli (Sigma-Aldrich, Inc., St. Louis, MO, USA), as previously described ( 32 – 34 ), or in the presence of heat-killed B. abortus (multiplicity of infection [MOI] of 100:1) for 12 h. mRNAs of the stimulated or control cells were then isolated and subjected to gene expression analyses. In brief, mRNAs were purified with an Easypure RNA kit (TransGen Biotech, Inc., Beijing, China) and reverse transcribed into cDNA according to the manufacturer's instructions.…”

CCR5 and CCR5Δ32 in bacterial and parasitic infections: Thinking chemokine receptors outside the HIV box

“…Classically, three main species are responsible for infection in humans: Brucella melitensis , Brucella abortus and Brucella suis (Boschiroli, Foulongne, & O’Callaghan, 2001; Franco, Mulder, Gilman, & Smits, 2007), although Brucella canis can also infect humans (Bukhari, 2018). Monocytes and macrophages are the main replication sites of Brucella spp., being also their cellular reservoirs (Wang, Li, et al, 2017). Brucellosis is a febrile disease that, in some cases, is severe and debilitating (Boschiroli et al, 2001; Franco et al, 2007).…”