Cobalt (II) Chloride Regulates the Invasion and Survival of <i>Brucella abortus</i> 544 in RAW 264.7 Cells and B6 Mice

Abstract

The effects of Cobalt (II) chloride (CoCl2) in the context of Brucella abortus (B. abortus) infection have not been evaluated so far. Firstly, we found that CoCl2 treatment inhibited the phagocytosis of B. abortus into RAW 264.7 cells. The inhibition of bacterial invasion was regulated by F-actin formation and associated with a reduction in the phosphorylation of ERK1/2 and HIF-1α expression. Secondly, the activation of trafficking regulators LAMP1, LAMP2, and lysosomal enzyme GLA at the transcriptional level activated immune responses, weakening the B. abortus growth at 4 h post-infection (pi). The silencing of HIF-1α increased bacterial survival at 24 h pi. At the same time, CoCl2 treatment showed a significant increase in the transcripts of lysosomal enzyme HEXB and cytokine TNF-α and an attenuation of the bacterial survival. Moreover, the enhancement at the protein level of HIF-1α was induced in the CoCl2 treatment at both 4 and 24 h pi. Finally, our results demonstrated that CoCl2 administration induced the production of serum cytokines IFN-γ and IL-6, which is accompanied by dampened Brucella proliferation in the spleen and liver of treated mice, and reduced the splenomegaly and hepatomegaly. Altogether, CoCl2 treatment contributed to host resistance against B. abortus infection with immunomodulatory effects.

Keywords

• <i>Brucella abortus</i>
• CoCl₂
• HIF-1α
• immune response
• RAW 264.7 cell
• B6 mouse