Mycobacteria and allergies

Rook, G.A.W.; Hamelmann, Eckard; Brunet, Laura Rosa

doi:10.1016/j.imbio.2007.03.003

Cited by 26 publications

(24 citation statements)

References 94 publications

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“…Epidemiological studies in humans and experimental work in animals suggest that mycobacteria can modify allergen-induced airway inflammation [1]. Our present study further delineates this notion, showing that an inhibitory function of BCG might be mediated via modulation of DC, resulting in up-regulation of regulatory T cell function and down-regulation of Th2-type functionin vitro.…”

Section: Discussionsupporting

confidence: 77%

“…Epidemiological studies have described an inverse association between mycobacterial infection and atopy and asthma [1, 2]. The first report to create a lot of excitement about this topic illustrated that in Bacillus Calmette-Guérin (BCG)-vaccinated school children from an endemic tuberculosis region in Japan, skin test reactivity to tuberculin and asthma prevalence were inversely associated [3].…”

Section: Introductionmentioning

confidence: 99%

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BCG Priming of Dendritic Cells Enhances T Regulatory and Th1 Function and Suppresses Allergen-Induced Th2 Function in vitro and in vivo

Ahrens

Grüber²,

Rd³

et al. 2009

Int Arch Allergy Immunol

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Background: The inverse correlation of mycobacterial infection with asthma prevalence and the inhibitory effects of vaccination with Bacille Calmette-Guérin (BCG) on airway hyperreactivity in asthma models suggest modulation of dendritic cell (DC) and T cell functions by mycobacterial compounds. Methods: To delineate these immunological effects, the immunogenicity of BCG Copenhagen, BCG Chicago and BCG Pasteur was compared in a mouse model. Bone marrow-derived dendritic cells (BMDCs) from BALB/c mice were stimulated with ovalbumin (OVA) with or without BCG. BMDCs were phenotypically characterized by flow cytometry, and we used ELISA to measure the cytokine production of BMDCs as well as of co-cultivated allergen-specific T cells in response to OVA-pulsed. Immunomodulatory effects of BCG were studied in a model of allergic airway inflammation by adoptive transfer of allergen-pulsed BMDCs. Results: Immunomodulation with BCG induced production of IL-10 and IL-12 by BMDCs. Co-cultured allergen-specific T cells produced less IL-5, IL-13 and IFN-γ but more IL-10. Also the number of FoxP3⁺ regulatory T cells was enhanced. Strongest effects were seen with BCG Chicago and BCG Pasteur. In vivo, administration of BCG modulated OVA-pulsed BMDCs then reduced eosinophilic airway inflammation but enhanced infiltration with granulocytes. Airway hyperreactivity and mucus production were reduced and more FoxP3⁺ T cells were observed. Conclusion: BCG-induced suppression of Th2-type allergic airway inflammation was associated with enhancement of regulatory T cell function but also of Th1-associated neutrophilic airway inflammation. These findings raise concerns regarding the safety profile of BCG as a potential tool for prevention and therapy of allergic airway disease.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

BCG Priming of Dendritic Cells Enhances T Regulatory and Th1 Function and Suppresses Allergen-Induced Th2 Function in vitro and in vivo

Ahrens

Grüber²,

Rd³

et al. 2009

Int Arch Allergy Immunol

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“…The saprophytic mycobacteria are believed to play a protective role in chronic infections like asthma and TB [27]. However, clinical trials with saprophytic M. vaccae didn't benefit TB patients and led to local adverse reactions in recipients [28].…”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of a Leprosy Immunotherapeutic Bacillus Provides Insights into Mycobacterium Evolution

et al. 2007

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BackgroundEvolutionary dynamics plays a central role in facilitating the mechanisms of species divergence among pathogenic and saprophytic mycobacteria. The ability of mycobacteria to colonize hosts, to proliferate and to cause diseases has evolved due to its predisposition to various evolutionary forces acting over a period of time. Mycobacterium indicus pranii (MIP), a taxonomically unknown ‘generalist’ mycobacterium, acts as an immunotherapeutic against leprosy and is approved for use as a vaccine against it. The large-scale field trials of this MIP based leprosy vaccine coupled with its demonstrated immunomodulatory and adjuvant property has led to human clinical evaluations of MIP in interventions against HIV-AIDS, psoriasis and bladder cancer. MIP, commercially available as ‘Immuvac’, is currently the focus of advanced phase III clinical trials for its antituberculosis efficacy. Thus a comprehensive analysis of MIP vis-à-vis evolutionary path, underpinning its immanent immunomodulating properties is of the highest desiderata.Principal FindingsGenome wide comparisons together with molecular phylogenetic analyses by fluorescent amplified fragment length polymorphism (FAFLP), enterobacterial repetitive intergenic consensus (ERIC) based genotyping and candidate orthologues sequencing revealed that MIP has been the predecessor of highly pathogenic Mycobacterium avium intracellulare complex (MAIC) that did not resort to parasitic adaptation by reductional gene evolution and therefore, preferred a free living life-style. Further analysis suggested a shared aquatic phase of MAIC bacilli with the early pathogenic forms of Mycobacterium, well before the latter diverged as ‘specialists’.Conclusions/SignificanceThis evolutionary paradigm possibly affirms to marshal our understanding about the acquisition and optimization of virulence in mycobacteria and determinants of boundaries therein.

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“…Moreover, BCG protects against severe forms of childhood TB, especially meningeal and miliary TB. Usually, BCG vaccine induces also an acquired delayed type hypersensitivity (DTH) to mycobacterial tuberculin proteins [4,5]. Skin testing with purified tuberculin -PPD (purified protein derivative) is the only currently available method of detecting BCG-induced DTH, in vivo.…”

Section: Introductionmentioning

confidence: 99%

Monocyte response receptors in BCG driven delayed type hypersensitivity to tuberculin.

Strapagiel

Kasztalska²,

Druszczyńska³

et al. 2008

Folia Histochem Cytobiol.

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Tuberculosis (TB) still remains the leading cause of mortality due to bacterial pathogen. The only currently available vaccine against TB, Bacille Calmette-Guérin (BCG) is at best credited with a 50% overall protective efficacy. Skin testing with purified protein derivative (PPD) from Mycobacterium tuberculosis is the method of detecting BCG-induced cell mediated immunity, in vivo. In the previous study we found that approximately 60% young volunteers with no history of TB, who had been subjected to neonatal BCG vaccination and revaccination(s) at school age, developed delayed type hypersensitivity (DTH) to tuberculin. The remaining volunteers were persistently tuberculin negative. Moreover, we found a significant association between BCG driven development of DTH to PPD and the polymorphism within the CD14 C/T(-159) gene for macrophage receptor recognising mycobacterial compounds. It has suggested that the CD14 gene variants may play a role in the appearance and persistence of DTH to PPD in BCG vaccinated subjects. In order to extend our study on a possible role of CD14 in BCG driven DTH response to PPD, we measured the expression of mCD14 on macrophages, stimulated or not stimulated with mycobacterial antigens, and the serum levels of sCD14. Considering the importance of CD14 -TLR2/TLR4 interactions in macrophage signalling, we determined the polymorphism of TLR2 and TLR4 genes as well as macrophage expression of TLR2 for the volunteers with and without skin reactivity to PPD. We observed a subtle but significant decrease in CD14 density on adherent monocytes from tuberculin positive versus tuberculin negative volunteers. However, we found no difference in CD14 density on monocytes enriched in CD14+ cells using anti-CD14 mAb coupled to magnetic beads. A significant increase in CD14 density was observed on macrophages stimulated with PPD and LPS but not with live BCG bacilli. However, this increase as well as serum levels of soluble sCD14 were similar in the volunteers with and without skin reactions to PPD. Thus, our suggestion on the role of CD14 in the generation of DTH to tuberculin in BCG vaccinated subjects should be further explored. The most important CD14 co-receptors are Toll-like receptors (TLRs) which activate nuclear factors for the production of inflammatory cytokines. However, we could see no association between the polymorphisms of TLR4 (Asp299Gly and Thr399Ile) and TLR2 genes (Arg753Gln and Arg677Trp) and skin responses to PPD. Also, the TLR2 density was similar on monocytes from tuberculin negative and tuberculin positive volunteers.

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Mycobacteria and allergies

Cited by 26 publications

References 94 publications

BCG Priming of Dendritic Cells Enhances T Regulatory and Th1 Function and Suppresses Allergen-Induced Th2 Function in vitro and in vivo

BCG Priming of Dendritic Cells Enhances T Regulatory and Th1 Function and Suppresses Allergen-Induced Th2 Function in vitro and in vivo

Molecular Analysis of a Leprosy Immunotherapeutic Bacillus Provides Insights into Mycobacterium Evolution

Monocyte response receptors in BCG driven delayed type hypersensitivity to tuberculin.

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