Expression And Significance Of STING In The Peripheral Blood Of Patients With Acute And Chronic Brucellosis

Objective :To analyze and compare the expression of STING pathway-related genes and the expression of inflammatory cytokines TNF-α and IFN-β in peripheral blood of patients with acute and chronic brucellosis,and to analyze the correlation between the expression levels of each factor in pairs,and to explore the possible mechanism of STING receptor in different stages of brucellosis.This study provides clues for the further study of immunity and escape mechanism of brucellosis.Methods:A total of 50 patients diagnosed with brucellosis by the Inner Mongolia Center for Disease Control and Prevention from May 2022 to February 2023 were collected,including 30 patients in the acute phase and 20 patients in the chronic phase,and a total of 20 healthy individuals collected at the Affiliated Hospital of Inner Mongolia Medical University during the same period as healthy controls,and those enrolled signed an informed consent form to collect the information and enter it into the database.All participants were enrolled and 2ml of fasting elbow venous blood and 1ml of serum were collected in the early morning,and the expression of STING,TBK1,IRF3 and NK-κB genes in peripheral blood was measured using real-time fluorescence quantitative PCR,and the expression of TNF-α and IFN-β in peripheral blood was measured using ELISA kits in each group,and the relationship between STING and TBK1,IRF3 and IFN-β was analyzed.IRF3,IFN-β and the correlation between the expression of STING and NF-κb,TNF-α.Results:(1)The expression levels of STING were 0.86(0.72,1.04)in the acute phase,1.48(1.14,1.66)in the chronic phase and 1.30(1.02,1.50)in the healthy control group.Statistical results indicate that the expression of STING were higher in the chronic phase case group than in the acute phase case group and the control group,while the expression levels were lower in the acute phase case group than in the control group,with statistically significant differences(P < 0.05).TBK1 was expressed at 0.65(0.45,0.74)in the acute phase,0.72(0.49,1.01)in the chronic phase,and0.70(0.57,0.81)in the healthy control group,with statistically significant differences(P < 0.05).IRF3 expression levels were 1.15(0.94,1.49)in the acute phase,1.06(1.00,1.12)in the chronic phase and 1.02(0.92,1.10)in the healthy control group,all with statistically significant differences(P < 0.05).The trend of expression levels was higher in the chronic case group than in the acute case group and the control group,and lower in the acute case group than in the control group.NF-κb expression levels were 0.81(0.60,0.94)in the acute phase and 0.51 in the chronic phase(0.32,0.62)and in the healthy control group the expression level was 0.47(0.33,0.64).By statistical tests,the expression level was higher in the acute phase case group than in the chronic phase case group and control group,and the expression level was higher in the chronic phase case group than in the control group,and the differences were all statistically significant(P < 0.05).(2)The expression of TNF-α in the acute phase was 46.21 ± 6.26,in the chronic phase was 40.65±7.40,and in the healthy control group was 32.83±5.90.Statistical results indicate that the expression of TNF-α in the acute phase was higher than that in the chronic phase and the control group,and the expression level of TNF-α in the chronic phase was higher than that in the control group.The expression of IFN-β in the acute phase was 410.00±72.21,in the chronic phase was 566.88±76.67,and in the healthy control group was 462.88±68.68.Statistical results indicate that the expression in the chronic phase was higher than that in the healthy control group,and the expression in the acute phase was lower than that in the control group.(3)Spearman was used to analyze the relationship between STING with TBK1,IRF3,NF-κb,TNF-α,and IFN-β.Correlation analysis showed that the expression of STING were positively and weakly correlated with TBK1 and IFN-β,and the expression of STING were negatively and weakly correlated with NF-κb and TNF-a,and there was no correlation between STING and IRF3.Conclusion:STING may be involved in inhibiting the expression of TBK1 and IRF3 in the early stage of Brucella infection,which further hinders the effective activation of IFN-β and plays a role in negative regulation of immune response.This may be an immune escape mechanism of Brucella in the early stage of human infection.The increased expression of STING-TBK1-IRF3 pathway in the chronic phase may be due to the weakened inhibitory effect,and the specific regulation needs further study.The expression level of NF-κb is increased in the acute phase,which is opposite to the trend of STING expression level.It is speculated that in the acute phase,besides STING,there are other receptors that activate NF-κb to further secrete TNF-α and other inflammatory factors to promote bacterial clearance and inflammatory immune response,so as to control infection.