| Background:Brucella infection can be protected by specific immune escape mechanism and reproduce and survive in the phagocytes of the host.It can not only form local granuloma around the focus of infection,but also be carried by phagocytes to infect tissues and organs of the whole body,causing serious pathological changes and even death.The intracellular life style of brucella makes it difficult to completely remove brucella from the host,and causes a series of complex immune responses in the host.Helper T cells(Th)and their related cytokines and chemokines participate in the host immune defense against brucella,and interact with a variety of immune cells such as monocytes/macrophages(MO/M f)and NK cells to affect clinical manifestations and participate in the progression of the disease.However,the specific immune effects and mechanisms of various immune cell populations in the process of brucellosis infection are not completely clear.Purpose:1.To study the dynamic changes of Th1,Th17 and Th22 lymphocyte subsets and related cytokines in patients with brucellosis,and to explore the immune function and mechanism of Th22 lymphocyte subsets in brucellosis.2.To study the immune function and mechanism of chemokines and their receptors in the course of brucellosis.3.To study the differential expression of genes and proteins in immune cells and their role in the pathogenesis of brucellosis,and to explore the possible effect of immune exhaustion on the chronic progression of brucellosis.Methods:1.The phenotype and distribution of Th1,Th17 and Th22 lymphocyte subsets and the expression of related cytokines and chemokines in peripheral blood of patients with brucellosis were studied by flow cytometry.The levels of serum IFN-g,IL-17 and TNF-? cytokines were detected by Cytometric quantitative Bead quantitative Array(CBA),and the levels of serum IL-22 were determined by enzyme-linked immunosorbent assay(ELISA).The dynamic change trend of immune index was studied by follow-up.2.The expression profiles of T lymphocytes,monocytes / macrophages(MO/M f)and natural killer cell transcripts were determined by RNA sequencing(RNA-seq)and differential gene expression analysis.The expression levels of genes and proteins affecting immune function and the relationship between genes and proteins and the immune status of brucellosis were studied,and the results of transcriptome analysis were verified by q PCR method.3.To study the interaction mechanism between immune cells and analyze the correlation between differentially expressed genes.To explore the key factors that may affect the progress of chronic brucellosis.Results:The number of Th1 and Th17 lymphocytes in peripheral blood of patients with brucellosis increased in the early stage of infection,and Th1 maintained a high level in the acute stage of brucellosis(within 6 months).The high level expression of Th17 lymphocytes lasted for a short time.The distribution and activation of Th1 and Th17 cell subsets will affect the expression and activation of Th22 cells.In brucellosis,host Th22 lymphocytes play a role in protecting target organs against tissue damage,especially in bone and joint injuries caused by brucellosis.The number of Th22 lymphocytes in the acute phase of brucellosis showed an overall decreasing trend,so it is prone to bone and joint injury after brucellosis infection.Brucella infection impairs the chemotactic function of many kinds of immune cells of the host,which leads to the weakening of the recruitment function of immune cells to the infected site.After Brucella infection,the expression of inhibitory receptor molecules in T cells,MO/M cells and NK cells increased,which could regulate the decrease of the expression of many chemokines and receptors,and reduce the number of immune cells recruited to the focus.And inhibitory receptor molecules can also cooperate with each other to inhibit the function of activated immune cells in patients with brucellosis,induce the occurrence of immune exhaustion in the focus,and promote the progression of brucellosis to a chronic course of disease.Conclusion:1.The number of Th1 and Th17 lymphocytes in peripheral blood of patients with brucellosis increased in the early stage of infection,and Th1 maintained a high level in the acute stage of brucellosis(within 6 months).The high level expression of Th17 lymphocytes lasted for a short time.The distribution and activation of Th1 and Th17 cell subsets will affect the expression and activation of Th22 cells.In brucellosis,host Th22 lymphocytes play a role in protecting target organs against tissue damage,especially in bone and joint injuries caused by brucellosis.The number of Th22 lymphocytes in the acute phase of brucellosis showed an overall decreasing trend,so it is prone to bone and joint injury after brucella infection.2.Brucella infection impairs the chemotactic function of many kinds of immune cells of the host,which leads to the weakening of the recruitment function of immune cells to the infected site.3.After Brucella infection,the expression of inhibitory receptor molecules in T cells,MO/M cells and NK cells increased,which could regulate the decrease of the expression of many chemokines and receptors,and reduce the number of immune cells recruited to the focus.And inhibitory receptor molecules can also cooperate with each other to inhibit the function of activated immune cells in patients with brucellosis,induce the occurrence of immune exhaustion in the focus,and promote the progression of brucellosis to a chronic course of disease. |
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