Ex vivo production of interferon-γ, tumor necrosis factor-α, and interleukin-6 by mouse macrophages during infection with M. bovis and M. tuberculosis H37Rv

Chernousova, L. N.; Smirnova, Tatiana G.; Afanasieva, E. G.; Карпов, В.Л.; Timofeev, A.

doi:10.1007/s10517-007-0412-4

Cited by 4 publications

(2 citation statements)

References 6 publications

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“…IFN-γ production induced by M. tuberculosis is 4-fold greater than that induced by BCG,24 so we can speculate that M. tuberculosis culture supernatants or heat-killed preparations would be more effective for suppressing asthmatic reactions than those of BCG. However, this was not the case in the present study, and there were no differences between them.…”

Section: Discussionmentioning

confidence: 93%

Preventive effects of mycobacteria and their culture supernatants against asthma development in BALB/c mice

Han

Choi

Eom

et al. 2010

Allergy Asthma Immunol Res

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PurposeLive Mycobacterium bovis Bacille Calmette-Guérin (BCG) has a suppressive effect on asthma, but its use in clinical practice may be limited due to adverse reactions. To develop a product that is effective for suppressing asthma with minimal adverse reactions, we investigated whether the heat-killed body or culture supernatants of mycobacteria could also prevent asthma development.MethodsFemale BALB/c mice were treated with live BCG, the heat-killed body, or culture supernatants of BCG or Mycobacterium tuberculosis intraperitoneally, while sensitizing and provoking with ovalbumin. Then they underwent a methacholine bronchoprovocation test, and the peribronchial inflammatory cell numbers and cytokine levels in splenocyte culture supernatants were assessed.ResultsThe airway sensitivity to methacholine decreased significantly after treatment with not only live BCG (30.8 versus 10.0 mg/mL, P<0.001) but also with the culture supernatant (BCG, 23.0 mg/mL, P<0.05; M. tuberculosis, 20.5 mg/mL, P<0.05). In contrast, heat-killed mycobacteria did not effectively decrease airway sensitivity. The peribronchial eosinophil counts and the goblet cell proportions in total epithelial cells decreased significantly in most of the groups. The interferon-γ/interleukin-5 ratios increased significantly in most of the treatment groups except for the heat-killed groups, and were significantly related to airway sensitivity (r=0.312, P<0.01) and peribronchial eosinophil counts (r=-0.416, P<0.001). Interleukin-17A level was inversely related to airway sensitivity (r=-0.212, P<0.05) and was significantly lower in the live BCG group than in the control (137±20 versus 308±57 pg/mL, P<0.05).ConclusionsBCG and mycobacteria culture supernatants may effectively prevent the development of asthma associated with altered Th1/Th2 cytokines and interleukin-17A levels.

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Section: Discussionmentioning

confidence: 93%

Preventive effects of mycobacteria and their culture supernatants against asthma development in BALB/c mice

Han

Choi

Eom

et al. 2010

Allergy Asthma Immunol Res

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“…In this study, 38-kDa protein and Ag85 of M. tuberculosis suppressed all three components of AHR (airway sensitivity, excessive airway narrowing, and airway reactivity), while MPB70 of BCG suppressed only airway sensitivity. Because M. tuberculosis induces the production of four times more IFN-γ than does BCG,39 we speculated that secretory proteins of M. tuberculosis would induce the production of greater amounts of IFN-γ than do BCG proteins, but this was not the case. The IFN-γ/IL-5 ratio was higher in the MPB70-treated group than in the Ag85-treated group in this study.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effects of Mycobacterial Secretory Proteins Against Established Asthma in BALB/c Mice

Han

Choi

et al. 2012

Allergy Asthma Immunol Res

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Purpose Live/killed mycobacteria and culture supernatants can suppress asthmatic reactions. This study investigated whether mycobacterial secretory proteins have therapeutic effects on asthma. Methods Mycobacterium bovis bacille Calmette-Guérin (BCG; 2×10 5 CFUs) and mycobacterial secretory proteins (Ag85 complex, 38-kDa protein or MPB70; 4 or 20 µg) were administered intraperitoneally to female BALB/c mice with established airway hyperresponsiveness. One week after treatment, the mice underwent a methacholine challenge test, and then inflammatory cell numbers in bronchoalveolar lavage fluid (BAL) and around bronchi (<500 µm), and cytokine levels in splenocyte supernatants, were assessed. Results BCG and all of the tested secretory proteins significantly improved airway sensitivity compared to baseline values ( P <0.05). The secretory protein Ag85 complex significantly suppressed airway reactivity also ( P <0.05), while 38-kDa protein significantly suppressed reactivity and maximal narrowing ( P <0.05). The number of eosinophils in BAL and around bronchi, and the goblet cell proportion, were also significantly reduced in mice in both the BCG and secretory protein groups compared to the asthma control group. IFN-γ/IL-5 ratios were significantly higher in mice treated with BCG, 4 µg MPB70 or 4 µg 38-kDa protein than in asthma control mice ( P <0.05), and were negatively associated with airway hyperresponsiveness, peribronchial eosinophil numbers and goblet cell proportion (all P <0.05). IL-17A was positively correlated with IL-5 (r=0.379, P <0.001), maximal airway narrowing, peribronchial eosinophil numbers and goblet cell proportion (all P <0.05). Conclusions Secretory proteins from BCG and M. tuberculosis and live BCG were effective against established asthma, their effects being accompanied by increased IFN-γ/IL-5 ratios. Thus, allergic asthma could be effectively treated with mycobacterial secretory proteins.

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De novo histidine biosynthesis protects Mycobacterium tuberculosis from host IFN-γ mediated histidine starvation

et al. 2021

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Intracellular pathogens including Mycobacterium tuberculosis (Mtb) have evolved with strategies to uptake amino acids from host cells to fulfil their metabolic requirements. However, Mtb also possesses de novo biosynthesis pathways for all the amino acids. This raises a pertinent question- how does Mtb meet its histidine requirements within an in vivo infection setting? Here, we present a mechanism in which the host, by up-regulating its histidine catabolizing enzymes through interferon gamma (IFN-γ) mediated signalling, exerts an immune response directed at starving the bacillus of intracellular free histidine. However, the wild-type Mtb evades this host immune response by biosynthesizing histidine de novo, whereas a histidine auxotroph fails to multiply. Notably, in an IFN-γ−/− mouse model, the auxotroph exhibits a similar extent of virulence as that of the wild-type. The results augment the current understanding of host-Mtb interactions and highlight the essentiality of Mtb histidine biosynthesis for its pathogenesis.

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Ex vivo production of interferon-γ, tumor necrosis factor-α, and interleukin-6 by mouse macrophages during infection with M. bovis and M. tuberculosis H37Rv

Cited by 4 publications

References 6 publications

Preventive effects of mycobacteria and their culture supernatants against asthma development in BALB/c mice

Preventive effects of mycobacteria and their culture supernatants against asthma development in BALB/c mice

Therapeutic Effects of Mycobacterial Secretory Proteins Against Established Asthma in BALB/c Mice

De novo histidine biosynthesis protects Mycobacterium tuberculosis from host IFN-γ mediated histidine starvation

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