Yunzhi Peng; Wenhui Bai; Zhanli Wang; Hui Yu
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) ...
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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.
Abstract
Background: Interleukin-10 (IL-10) is a Th2-type cytokine that inhibits macrophage activation. It is known that production of IL-10 is affected by its gene promoter polymorphisms. Objective: To investigate the relationship between IL-10 gene promoter polymorphisms and susceptibility to brucellosis. ...
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Background: Interleukin-10 (IL-10) is a Th2-type cytokine that inhibits macrophage activation. It is known that production of IL-10 is affected by its gene promoter polymorphisms. Objective: To investigate the relationship between IL-10 gene promoter polymorphisms and susceptibility to brucellosis. Methods: One hundred and ninety patients with brucellosis and 81 healthy animal husbandmen who owned infected animals and consumed their contaminated dairy products were included in this study. All individuals were genotyped for three bi-allelic IL-10 gene promoter polymorphisms at positions -1082(G/A), -819(T/C), and -592(A/C) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The distribution of C alleles at positions -592 and -819 of IL-10 were significantly higher in patients than in the healthy animal husbandmen (p=0.034 and p=0.0086, respectively). IL-10 ATA single and double haplotypes were significantly higher in controls, compared to the patients (p= 0.0278 and p=0.013, respectively). Conclusion: According to the results higher frequency of C alleles at positions -592 and -819 of IL-10 in patients may be considered as genetic factors for susceptibility to brucellosis.
Manoochehr Rasouli; Simin Kiany; Abdolvahhab Alborzi
Volume 2, Issue 4 , December 2005, , Pages 226-231
Abstract
Background: Brucella is a gram-negative bacterium, causing acute and chronic infection in humans and animals. Cell-mediated immunity is the main protective immune response against Brucella spp. Activation of macrophages by IFN-γ and generation of reactive oxygen intermediates and nitric oxide are ...
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Background: Brucella is a gram-negative bacterium, causing acute and chronic infection in humans and animals. Cell-mediated immunity is the main protective immune response against Brucella spp. Activation of macrophages by IFN-γ and generation of reactive oxygen intermediates and nitric oxide are the main immunologic mechanisms responsible for control of Brucella infection. Objective: To investigate the correlation between IFN-γ gene polymorphism and brucellosis. Methods: 195 patients with brucellosis, 186 healthy patients' family members and 82 healthy farmers who kept infected animals and consumed their contaminated dairy products were selected to take part in the study. IFN-γ genotyping at position +874 (T→A) was carried out by allele specific polymerase chain reaction (AS-PCR) method. Results: The frequency of AT and TT genotypes significantly increased in farmers compared to patients with brucellosis (P=0.03) while there was no significant difference in genotype distribution between patients and their healthy family members. Conclusion: IFN-γ (+874) AA genotype is probably a genetic factor that contributes to the susceptibility of the individuals to brucellosis.
