| This topic from the body (pulmonary tuberculosis, latent tuberculosis patients and healthy people) on cell subsets level, cellular level, molecular level study on the level of zinc ion abundance and zinc transporter ZIP2 in the body against Mycobacterium tuberculosis (Mycobacterium tuberculosis, MTB) immune response generated by the role, and observed the difference of latent pulmonary tuberculosis tuberculosis patients on zinc and zinc ion content of active pulmonary expression of zinc, understanding whether the expression of Mycobacterium tuberculosis pathogenesis and contact whether. We further discuss whether to search for human infection of tuberculosis, TB etiology immune system found a new molecular target for the treatment of position and effect index provides theory and technology basis.According to WHO statistics, there are about about 2000000000 people worldwide infected with MTB, approximately 880 000 new cases and 2000000 deaths each year. TB has become the current threats to human life and health of serious infectious diseases. Is a public health problem in the world.The body of infection of Mycobacterium tuberculosis (Mycobacterium tuberculosis, MTB), part of the crowd did not appear clinical symptoms and the formation of latent tuberculosis infection (latent tuberculosis infection, LTBI). Many domestic and foreign research shows that, LTBI is likely to develop active tuberculosis patients for 4%-11%, especially after the infection risk of two years before the greater. These groups, there may be a change of about 10% of the people for active tuberculosis patients, in which 10% people, half of the infected people in front of the annual incidence of 2-4 after infection; half the population left, when the body’s immunity decline, will be in the future when any disease. Therefore, LTBI has become one of the important sources of tuberculosis patients.Zinc (Zinc, Zn) is a kind of important trace element for organism must, generally exist as zinc ion state. It is used as an auxiliary factor of more than 50 kinds of enzyme and 300 kinds of coenzyme, participating in a wide range of human metabolism, gene transcription, cell growth, differentiation and maturation. According to the domestic and foreign reports we know that, in the human gene pool of approximately 10% protein is a zinc correlation binding protein, many life processes are closely dependent on the process of zinc, zinc and so became known as the "elements of life". Zinc and immune system function are closely related, not only can promote the mitosis of lymphocyte, T lymphocyte, monocyte macrophage, increase the quantity and vitality, enhance the body resistance to infection, but high levels of zinc ion, also have a greater toxicity. Zinc concentration in normal body cells in a steady state, if the concentration of steady state for some reason imbalance, will lead to disease occurrence of multiple systems including the immune system. It has been shown that, zinc deficiency can cause the atrophy of thymus cells, thymus hormone secretion decreased, T cell immune dysfunction and cell mediated down-regulation occurs.Zinc concentration within the cell is the basic factor to keep the body re distribution of zinc homeostasis, but cannot free zinc ions through the cell membrane, only in a class called zinc transporters (Zinc transporter) special assistance to complete membrane protein. In mammals, this class of proteins including 2 family members:zinc regulation like protein (Zrt- and Irt-like proteins, ZIP) family and the cation diffusion facilitator factor (cation diffusion facilitator, CDF) family (also known as the ZnT family). Having the opposite effect of these two kinds of zinc transporters in cells, the outer.zinc transport direction and path:ZIP can increase the zinc uptake or promote the internal flow of organelles Zn release, to increase the content of zinc in the cytoplasm, and ZnT can promote the outflow of cytoplasmic zinc and zinc change make room area in various organelles, thus reducing the content of cytosolic zinc. In particular hZIP2 was discovered in 2000 by the first human specific uptake of zinc ion transporter.When the body after MTB infection, the body will start a series of complex immune response mechanism immediately, with intrusion to fight or kill the bacteria:first, MTB gradually into monocyte macrophages, the cells in the human body is the main target cells play a non specific immune response. Mononuclear macrophage and can be used as antibody antigen presenting cells, T lymphocyte stimulating promoter specific immune response mediated hypersensitivity Ⅳ:cytotoxic T cells induced by CD8+(CTL) by identifying the target cell, the release of perforin and (or) granulysin induced cell apoptosis such as dissolution, damage MTB growth environment, the additional antigen presenting plays the role of immune surveillance; helper T cell CD4+(TH) by secreting various cytokines influence the type and intensity of the immune response. According to the secretion of cytokines of different, can be divided into Th1, Th2 two kinds of functional subsets. The use of interferon gamma (IFN-gamma) Th1 type cytokine mainly play a protective immune responses. Th2 type cytokine upregulation would inhibit INF-gamma generation such as macrophages, NK cells, decreased the phagocytic killing ability of MTB, thus weakening the body protective immune response. In the process of occurrence and development of Th1, Th2 in the inflammatory cytokines can balance, there will be different results of anti infection or tissue damage, thereby affecting the outcome of patients with tuberculosis disease process. Thl cell immune response ability is low or deficiency is the most significant feature of cellular immunity in patients with tuberculosis.Although the global nearly 1/3 of the population infected with MTB, but in the end, only 10% of them develop tuberculosis. If the response of the anti MTB immune system is poor or inadequate, TB in vivo may lead to further the pathogenesis or forming a latent infection state for a long time. Results show that, the cellular immune function of patients with tuberculosis, low content of zinc in the blood than the normal population are low. Visible, zinc ions played a key role in the patients with tuberculosis immune system response, and zinc transporter function and regulation of zinc levels in the body it is closely related.Our previous study found that:compared with the healthy group, the serum zinc levels in patients with active pulmonary tuberculosis decreased, peripheral blood mononuclear cells (PBMC) ZIP2 mRNA expression, protein levels were increased obviously, knockdown of ZIP2 gene expression after the use of SiRNA technology, the expression level of PBMC in patients with active pulmonary tuberculosis ZIP2 mRNA decreased, IFN-gamma and closely related to the decreased expression of. Therefore, we speculate that there may be ZIP2 and zinc concentration of immune system in patients with tuberculosis response played an important role in the. By searching, we found that the domestic, outside there is no discussion on zinc transporter and tuberculosis patients with low levels of zinc, low immune function relationship between. Similarly, no study on the effect of tuberculosis patients in zinc transporter ZIP2 in anti Mycobacterium tuberculosis in immune response.Therefore, it is very necessary to based on some previous research, to further explore the immune responses in human zinc transporter ZIP2 in the body for the MTB generated from the human immune cell subsets level, cell level and molecular level. We hypothesize that:if different individuals in contact with MTB, their incidence or not or pulmonary tuberculosis this difference is mainly due to the different individuals of the abnormal expression of ZIP2 and low level of zinc caused by abnormal immune system response caused by, then ZIP2, zinc levels is likely to be one of the predisposing factors in the population of MTB; if established, immunological mechanism so that we can from a new perspective of proven pulmonary tuberculosis; also can be ZIP2 and zinc as the observation index of tuberculosis treatment targets and therapeutic efficacy of a new, so as to guide the clinical treatment effect and prognosis were evaluated and more accurate to the tuberculosis patient.ResultsSubgroup level and the 2 point of view the issue from the human immune cells, with the science and technology of molecular biology experiment, to study the expression of ZIP2 in different diseases, tuberculosis patients confirmed differences in Zn abundance and ZIP2mRNA and other diseases.The subjects were divided into 3 groups, active pulmonary tuberculosis group (Pulmonary tuberculosis, APTB), latent tuberculosis group, healthy control group (Control). APTB diagnosis of group according to national health standard of the industry, the healthy control group required no TB contact history. For the healthy control group can be divided into latent tuberculosis group and normal control group. Of the 3 groups of subjects after informed consent, from peripheral venous anticoagulant blood tests were as follows:(1) the content of zinc in plasma; (2) using BD Cytometric Bead Array America company (CBA) kit, detection of peripheral blood samples for serology three research groups of objects in IL-2, IL-4, IL-5, IL-10, TNF, IFN-gamma consists of 6 types of Th1/Th2 cell factor. (3) the study by real-time fluorescence quantitative PCR technology, the APTB, LTBI, Control between the three groups on ZIP2 relative expression levels were measured. (4) using flow cytometry to helper T lymph group subjects CD4+ fine sorting, real-time fluorescence quantitative PCR detection and ZIP2 index. (5) the crosswise contrast group APTB PBMC and CD4+ in peripheral blood T lymphocyte of ZIP2 level.Using SPSS statistical software, on the indexes of each index, correlation between group differences between cells and within the group type analysis.ConclusionThe concentration of IL-10 in APTB group was higher than that in LTBI group and Control group, a statistically significant difference (P<0.05), IL-10 showed low concentration levels between LTBI group and Control group, significant difference between the two groups and no significant; (2) IFN- gamma in group APTB (P=0.001) and LTBI (P<0.05) concentration levels showed high group, compared with the Control group, significant difference between the two groups was significant. In addition, IFN-levels in group APTB than in group LTBI is higher, and between the two groups with statistical difference (P<0.05). Peripheral blood PBMC APTB group in the ZIP2 levels were significantly higher than that of LTBI and Control two groups, the difference is statistically significant (P=0.001),LTBI and Control ZIP2 of the two groups the same level, no statistically significant difference. CD4+T lymphocytes of peripheral blood APTB group, the ZIP2 level was significantly higher than that of LTBI and Control two groups, the difference is statistically significant (P=0.001), LTBI and Control ZIP2 of the two groups the same level, no statistically significant difference. Expression of CD4+ in T lymphocytes of ZIP2 high level, is likely to be a major role in causing PBMC ZIP2 high level expression. APTB group of peripheral blood serum zinc levels were significantly lower than the LTBI and Control two groups, the difference is statistically significant (P<0.05); while the LTBI than the Control group, the serum zinc concentration is also slightly low, but significant difference is not obvious.On three groups of the research object analysis, we obtained the level of zinc ion active pulmonary tuberculosis group decreased significantly, but the latent tuberculosis patients with zinc levels compared to normal healthy people slightly low, but no statistical significance. Results show that zinc levels may be an important factor in whether the incidence of Mycobacterium tuberculosis infection after the body. We found that the level of ZIP2 expression of IL-10, PBMC, ZIP2 levels in CD4+ T lymphocytes or content of active pulmonary tuberculosis group than in the other two groups of high, while the PBMC, CD4+ T lymphocytes immune, particularly is an important link of cellular immunity induced by Mycobacterium tuberculosis infection after the body, therefore suggesting that there may be zinc deficiency state of immune cells cause tuberculosis is not easy to control, the development of active pulmonary tuberculosis. |
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