Iranian Journal of Immunology

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

Document Type : Original Article

Authors

Yunzhi Peng 1
Wenhui Bai 1
Zhanli Wang 1
Hui Yu 1, 2

1 Inner Mongolia Key Laboratory of Disease-Related Biomarkers, Baotou Medical College, Baotou 014060, China.

2 School of Basic Medicine, Baotou Medical College, Baotou 014060, China.

https://doi.org/10.22034/iji.2021.84578.1665
Abstract
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
Iranian Journal of Immunology
Volume 18, Issue 4
Autumn 2021
Pages 268-278

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