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The objective of this study was to investigate the effect of Mycobacterium vaccae on Jagged 1 and gamma delta T17 (γδT17) cells in asthmatic mice. An asthma mouse model was established through immunization with ovalbumin (OVA). Gamma-secretase inhibitor (DAPT) was used to block the Notch signaling pathway. M. vaccae was used to treat asthma, and related indicators were measured. Blocking Notch signaling inhibited the production of γδT17 cells and secretion of cytokine interleukin (IL)-17, which was accompanied by a decrease in Jagged1 mRNA and protein expression in the treated asthma group compared with the untreated asthma group. Similarly, treatment with M. vaccae inhibited Jagged1 expression and γδT17 cell production, which was associated with decreased airway inflammation and reactivity. The Notch signaling pathway may play a role in the pathogenesis of asthma through the induction of Jagged1 receptor. On the other hand, the inhibitory effect of M. vaccae on Jagged1 receptor in γδT17 cells could be used for the prevention and treatment of asthma.
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Animals , Rabbits , Signal Transduction , Mycobacterium , Ovalbumin , Receptors, Notch , Jagged-1 ProteinABSTRACT
Objective To investigate the cross-reactive immune responses to Mycobacterium vac-cae (M. vaccae), Mycobacterium tuberculosis (M. tuberculosis, H37Rv) and Mycobacterium bovis Bacillus Calmette-Guerin ( BCG) for providing reference for the development of new vaccines with M. vaccae. Meth-ods M. vaccae (ATCC95051), M. tuberculosis (H37Rv) and BCG (China strain) were cultured on L-J solid media and harvested. Total bacterial protein antigens prepared by ultrasonic disruption were used to im-munize BALB/c mice. IgG antibodies in serum samples were detected with enzyme-linked immunosorbent assay ( ELISA) to evaluate humoral immune responses. Cellular immunity was assessed by detecting various cytokines with cytokine release assay ( CRA) . Results The mice that were respectively immunized with the three mycobacterial antigens could produce high titers of antibodies ( IgG) and high levels of IFN-γand IL-2, but low levels of IL-4 and IL-10. Results of the cross reactivity tests showed that ATCC95051, H37Rv and BCG were able to cross-react with the immunized mice, and all of them induced high levels of IFN-γ, IL-2 and IgG antibodies. Conclusions The three Mycobacteria mainly elicited Th1 immune responses. There were cross-reactive immune responses to M. vaccae, M. tuberculosis and BCG, which might provide ref-erence for using M. vaccae in the development of new anti-tuberculous vaccines.
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Mycobacterium (M.) vaccae is a fast-growing species of saprophytic bacteria that is widely distributed. To understand the host immune responses induced by M. vaccae isolated from bovine submaxillary lymph nodes, C57BL/6 mice were infected with reference strain M. vaccae Bacillus Calmette-Guérin (BCG) and isolated M. vaccae using intraperitoneal injections. Comparison of the bacterial replication and organ pathology between M. vaccae and M. vaccae BCG revealed that M. vaccae was more malignant than M. vaccae in mice. We also demonstrated that serum from the M. vaccae-infected mice contained a higher expression level of gamma-interferon (IFN-γ), tumor necrosis factor alpha, monocyte chemoattractant protein-1, interleukin (IL)-4, IL-12, IL-10 and transforming growth factor beta than did the other groups, especially after week 4. Furthermore, when the numbers of CD3⁺CD4⁺IFN-γ⁺ and CD3⁺CD4⁺IL4⁺ cells in the infected mice were observed by flow cytometry, we found that a powerful T helper 1 (Th1) response was induced by M. vaccae infection, which was associated with the emergence of CD3⁺CD4⁺IFN-γ⁺ cells. However, the Th1 response declined over time, which was associated with appearance of the CD4⁺CD25⁺FoxP3⁺ and CD4⁺CD25⁺CD152⁺Treg cell reaction. In addition, a strong Th2 response was found. Finally, we found that M. vaccae infection increased the production of type I IFNs, which was associated with a reduced Th1 response.
Subject(s)
Animals , Mice , Bacillus , Bacteria , Chemokine CCL2 , Flow Cytometry , Injections, Intraperitoneal , Interferon-gamma , Interleukin-10 , Interleukin-12 , Interleukins , Lymph Nodes , Mycobacterium bovis , Mycobacterium , Pathology , Transforming Growth Factor beta , Tumor Necrosis Factor-alphaABSTRACT
Objective To investigate the effect of Mycobacterium vaccae vaccine combined with chemotherapy on immune function in treatment of children with pulmonary tuberculosis.Methods 89 cases with pulmonary tuberculosis from December 2010 to December 2013 treated in three hospitals in xinxiang city were randomly divided into control group and observation group.The control group was given regular chemotherapy,the observation group was given chemotherapy combined with Mycobacterium vaccae vaccine therapy.CD4 +,CD8 +,CD8 +/CD4 +and CD16 +CD56 +in peripheral blood were evaluated by FCM before and after treatment.Serum TNF- αand IL-10 levels were detected by the method of ELISA.Taking 3 sputum samples (night sputum,morning sputum and sputum at moment)of each patient to smear after treatment.Results Before treatment,there was no significant difference of each index between two groups.After treatment,CD4 +,CD4 +/CD8 +and CD16 +CD56 +in the observation group were significantly higher than that before treatment and the control group(P<0.05).The proportion of CD8 +in two groups was significantly lower than before treatment(P<0.05),the difference between groups was not statistically significant.Serum TNF- αand IL-10 levels decreased significantly in two groups than those before treatment and the control group(P<0.05).After treatment,the negative conversion rate in the control group was 90.9%(n=40),while 100%(n=45)in the observation group.The difference between two groups was statistically significant(P<0.05).Conclusion Mycobacterium vaccae vaccine combined with chemotherapy has a significant effect on children with pulmonary tuberculosis.It could significantly improve the immune function of children.
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Objective To investigate the effect and safety of Mycobacterium vaccae vaccine ( M. vaccae vaccine) on diabetes patients complicated with pulmonary tuberculosis. Methods A total of 76 diabetes patients complicated with pulmonary tuberculosis were randomized into immunotherapy group (M, n =38) and control group (C, n =38). Administration of routine anti diabetic drugs and diet treatment were conducted in both groups. In addition, patients in group M were treat with additional M. vaccae vaccine for 3 months, but those in group C were not. Results At the end of the treatment, no side effects of M. vaccae vaccine were found in group M, but immunological function of T cells was significantly improved. Compared with those in group C, CD3 and CD4 in group M were significantly higher ( P
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Objective:To study the effects of Mycobacterium vaccae vaccine on eosinophil apoptosis,protein expression of Fas and bcl-2 in lung tissues of asthmatic guinea pig.Methods:30 guinea pigs were randomly divided into NS,asthma and Mycobacterium vaccae vaccine group.A guinea pig model of asthma was estbalished with OVA(ovalbumin).Each guinea pig of Mycobacterium vaccae vaccine group was injected intramuscularly with 22.5?g of Mycobacterium vaccae vaccine 10 days before OVA immunization.After the last challenge,TdT-mediated dUTP nick end labeling (TUNEL)technique was used to determine the apoptosis of eosinophils and immunohistochemistry method was used to determine protein expression of Fas and bcl-2 in lung tissue sections.Results:Guinea pigs of Mycobacterium vaccae vaccine group had a higher AI(apoptosis index) of eosinophils in lung tissues[(23.8?5.4)%]than that of asthma group[(4.6?0.7)%,P
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Aim To study the immunoregulatory effect of Mycobacterium vaccae vaccine on asthmatic guinea pig.Methods 30 guinea pigs were randomly divided into NS,asthma and Mycobacterium vaccae vaccine groups. A guinea pig model of asthma was formed with ovalbumin.Every guinea pig of Mycobacterium vaccae vaccine group was intramuscularly injected with 22.5 ?g Mycobacterium vaccae vaccine 10 days before ovalbumin immunization.mRNA expressions of IL-4,IL-5 and IFN-? in lung tissue,total IgE and ovalbumin-specific IgE in serum were determined. Results For Mycobacterium vaccae vaccine group guinea pigs, mRNA expressions(optical density value) of IL-4(0.060?0.018) and IL-5(0.052?0.006)in lung tissue were significantly lower than those of asthma group(0.111?0.025,0.106?0.030 respectively; both P