Background:

It was reported that targeting the Toll-like receptor9 (TLR9) signaling pathway can be a promising therapeuticstrategy forinterventions in various inflammatory and infectiousdiseases. However,it was not known whether the human TLR9 isresponsive to Brucellacytidine-phosphate-guanosine (CpG) DNAsequences and activatesthehost’s innate immune system.


Objective:

The present study aimed to identify the novel humanTLR9agonists from Brucella CpG oligodeoxynucleotide(ODN) candidatesand verify their immune response regulatorymechanisms.


Methods:

Molecular docking methods were used to discover potentagonists of the human TLR9. The potential molecules were furthervalidated by Western blot and enzyme-linked immunosorbentassay(ELISA).


Results:

The experiment results showed a strong interactionandgood compatibility between the human TLR9 and BrucellaODN-1molecule. In addition, the induction of immune response byBrucella ODN-1 is a CpG-specific response. Moreover, the effectsof Brucella ODN-1 on cytokine response are dependent on theTLR9-mediated NF-κB pathway.


Conclusion:

These results indicated that the Brucella ODN-1 molecule canserve as a starting point to discover or designmore potent and specific TLR9 agonists that have the potential usein the treatment of Infectious diseases.


Keywords:

Agonist; Brucella; Cytidine-phosphateguanosine (CpG) motif; Toll-like receptor 9.



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TLR9/NF-kB Pathway Regulates Brucella CpG DNA-mediated Cytokine Response in Human Peripheral Blood Mononuclear Cells

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