Characteristics Of Immune Cells And Cytokines In Diabetes Patients With Tuberculosis

Diabetes mellitus(DM)is a metabolic disease characterized by hyperglycemia,and tuberculosis(TB)is an infectious disease caused by Mycobacterium tuberculosis.Previous studies have found that the probability of TB complications in DM patients is three times that of non-DM patients.The main reason is that high blood sugar damages the immune system of the human body,which makes a large number of latent TB-infected people turn into active TB patients,and ultimately leads to a low cure rate,high mortality rate,and poor prognosis in patients with diabetes and tuberculosis(TB-DM).However,the immunological characteristics of patients with TB-DM are still unclear.This study aims to provide a new strategy for early prevention and treatment of TB-DM patients by analyzing the immunological characteristics of patients with TB-DM.To this end,we conducted a cross-sectional study at the Eighth Medical Center of the PLA General Hospital.A total of 67 subjects were included in this study and divided into three groups,including the healthy control(HC)(n=23),T2DM group(n=26),and TB-DM group(n=18).Whole blood samples and plasma were collected from each group.Flow cytometry and proteomics technology of micro-sample ultra-sensitive trgeted protein detection were used to investigate the immune cell and key cytokine profiles of patients with TB-DM from the cellular and molecular levels.The results of immune cell-related studies showed that:(1)the ratio of innate and adaptive immune cells:The ratio of total T lymphocytes(P=0.0078)and CD4~+T cells(P=0.0070)in the TB-DM group was significantly higher than that in HC group,while the ratio of NK cells(P=0.0020)in TB-DM group was significantly lower than that in HC group.(2)The absolute number of innate and adaptive immune cells:The absolute counts of NK cells(P=<0.0001 or P=0.0292),total T lymphocytes(P=<0.0001 or P=0.0018),and CD8~+T(P=0.0009 or P=0.0072)cells in TB-DM group were significantly lower than those in HC or T2DM group.In addition,the absolute counts of CD4~+T cells(P<0.0001)and B cells(P=0.0004)in the TB-DM group were significantly lower than those in the T2DM group.To further analyze the influence of cell number differences on cytokines among different groups,we analyzed the changes of 92inflammatory cytokines in the plasma of the three groups.Firstly,we analyzed the differentially expressed cytokines and found two down-regulated cytokines in the HC group compared with the T2DM group.Compared with the TB-DM group,20 up-regulated cytokines and six down-regulated cytokines were in the HC group.There were 15 up-regulated cytokines and six down-regulated cytokines in the T2DM group.We then compared 92 inflammatory cytokines among the three groups.Five cytokines were significantly overexpressed,and 15 were significantly underexpressed in the TB-DM group compared with the HC and/or T2DM groups.On this basis,we further analyzed the correlation between the above differentially expressed cytokines and found that STAMBP was positively correlated with AXIN1 in HC(P<0.0001,Y=0.6869x+4.710).In T2DM patients,ST1A1 was positively correlated with CASP-8(P<0.0001,Y=0.7944x+1.127),while TRANCE was negatively correlated with SCF(P=0.0104,Y=0.8068x+11.00).In TB-DM patients,STAMBP was significantly positively correlated with AXIN1(P<0.0001,Y=1.003x-0.03203),while TNFSF14 was significantly negatively correlated with FGF-19(P=0.0105,Y=1.163x+13.71).We further analyzed the signaling pathways of these different-expressed proteins using the KEGG database.We found two signaling pathways that affect cytokine secretion in TB-DM patients,among which the JAK-STAT signaling pathway can promote the secretion of CXCL9 and CXCL10,and the NF-κB signaling pathway can promote the secretion of IL-6.In summary,our study showed that the number and function of immune cells in the early stage of T2DM were not significantly affected by hyperglycemia.Still,with the continued development of the disease,the number and function of immune cells in TB-DM patients were reduced considerably,resulting in a decrease in the body’s ability to resist the invasion of MTB.In addition,we also found 22cytokines in the plasma of patients with TB-DM that were significantly different from the other two groups.