| Objective:To explore the possible involvement and the correlation between NLRP6,AIM2 and the expression levels of inflammatory cytokines in different stages of brucellosis,the m RNA expression of the NOD-like receptor protein-6(NLRP6),the absent in melanoma factor-2(AIM2)inflammasome and interleukin-18(IL-18)and interleukin-1β(IL-1β)in peripheral blood of patients with brucella in different stages of the disease were observed.It provides new clues for the studies of the pathogenesis and defense mechanism of brucellosis,and a possible theoretical basis for judging the course of brucellosis.Methods:A total of 40 patients with brucellosis who were diagnosed in the Center for Disease Control and Prevention of Inner Mongolia from May 2021 to December 2021 were collected as the case group research objects(according to the national diagnostic criteria for brucellosis WS269-2019),including 20 cases in the acute phase,and 20 cases in the chronic phase(according to the “2018 Expert Consensus on the Diagnosis and Treatment of Brucellosis”,the duration of acute phase less than 6 months,and the duration of chronic phase longer than 6months),20 healthy people from the Physical Examination Center in the Affiliated Hospital of Inner Mongolia Medical University during the same period as the control group who are age-and-sex-matched were collected.After signing the informed consent,1ml of fasting cubital venous blood and 0.5ml of serum were collected from the 60 subjects.The expression levels of NLRP6 and AIM2 at the m RNA level of all subjects were measured by q RT-PCR method,and the expressions of IL-18 and IL-1β in the serum of all subjects were measured by ELISA kits.All the data were calculated by SPSS 22.0 statistical software and then the Correlation of inflammatory receptor proteins NLRP6,AIM2 inflammasome and downstream inflammatory cytokines IL-18 and IL-1βwere analysed.Results:In this study,a total of 60 samples were collected,20 in the acute phase,20 in the chronic phase,and 20 in the control group.Chi-square test and variance analysis were performed on each group.The result showed that there was no statistically significant difference in gender and age among the samples in each group.The data measured in the samples are comparable.After the normality test and the homogeneity of variance test,the measured results of the three groups of samples did not conform to the normal distribution and the property of equal variance.The multi-sample nonparametric rank sum test was used to analyze whether the differences in the data between the groups were statistically significant,and the results were obtained that the average relative expression levels of NLRP6 m RNA levels in each group were3.16(2.09,3.82)in the acute phase,1.98(1.60,2.79)in the chronic phase,and 1.27(0.95,1.86)in the control group.The difference between the control group and the chronic stage group(Z=2.802P=0.015),the control group and the acute stage group(Z=4.803 P < 0.001)were statistically significant(P<0.05),but there was no statistically significant difference between the acute stage group and the chronic stage group(Z=2.001 P=0.136)(P>0.05).The average relative expression level of NLRP6 in acute and chronic stage cases group were higher than that in control group.The average relative expression levels of AIM2 m RNA levels in each group were 2.50(1.45,3.55)in the acute phase,2.19(1.10,3.28)in the chronic phase,and 1.17(0.75,1.59)in the control group.The difference between the control group and the chronic stage group(Z=3.124 P=0.005),the control group and the acute stage group(Z=4.319 P < 0.001)were statistically significant(P<0.05),but there was no statistically significant difference between the acute stage group and the chronic stage group(Z=1.195 P=0.696)(P>0.05).The average relative expression level of AIM2 in acute and chronic stage cases group were higher than that in control group.The average relative expression levels of IL-18 in each group were 26.83(0.01,89.80)in the acute phase,0.01(0.01,74.03)in the chronic phase,and 68.11(52.13,113.75)in the control group.The difference between the control group and the chronic stage group(Z=-3.335 P=0.002)were statistically significant(P<0.05),but there was no statistically significant difference between the acute stage group and the control group(Z=-2.235 P=0.076)(P>0.05).The average relative expression level of IL-18 in acute stage cases group was higher than that in chronic stage cases group.The average relative expression levels of IL-1βlevels in each group were 7.67(7.13,8.12)in the acute phase,7.48(7.26,7.67)in the chronic phase,and 0.01(0.01,0.01)in the control group.The difference between the control group and the chronic stage group(Z=5.185 P<0.001),the control group and the acute stage group(Z=5.886 P < 0.001)were statistically significant(P<0.05),but there was no statistically significant difference between the acute stage group and the chronic stage group(Z=0.701 P=1.000)(P>0.05).The average relative expression level of IL-1β in acute and chronic stage cases group were higher than that in control group.The results of Spearman correlation analysis showed that the expression of NLRP6 and AIM2 in chronic phase samples was correlated.The correlation coefficient r=0.465,which is mean the moderate correlation.Conclusion : The brucella can invade various systems after it infects the body,resulting in non-specific clinical manifestations.Its onset is imperceptible and easy to cause the protracted disease.,which is partly cuased by weak immunogenicity of Virulence factors.It is the comprehensive effect of the activation of the viarous inflammatory pathway,among which,NLRP6,an important member of the NOD-like receptor family,may play a role in suppressing immune regulation during the whole process of Brucella infection,and the cofactor AIM2 of the inflammatory pathway may also play a role in suppressing immune regulation of brucellosis throughout the whole process.The mechanism plays a negative regulatory role,which may be an immune escape mechanism for the long-term survival of Brucella in humans. |
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