Abstract
The only currently available anti-tuberculosis vaccine, Bacillus Calmette–Guérin (BCG), has been reported to also protect against unrelated diseases, including inflammatory diseases such as allergic asthma. Recombinant BCG strains that produce IL-18 have been shown to enhance Th1 responses over non-recombinant BCG and to reduce IL-5 production and bronchoalveolar eosinophilia in mice. However, their ability to decrease the immune polarization of human Th2 cells is not known. Here, we show that BCG and recombinant BCG producing human IL-18 (rBCG-hIL-18) induced the maturation of Der p 1-stimulated monocyte-derived dendritic cells (MD-DCs) from healthy controls and from patients allergic to house dust mites. After incubation with mycobacteria and Der p 1, MD-DCs produced significantly more IL-23 and IP-10 but had no effect on IL-12p70 or IL-10 production compared to Der p 1-pulsed MD-DCs in the absence of mycobacteria. In the presence of Der p 1, BCG- and rBCG-hIL-18-pulsed MD-DCs cocultured with naive, but not with memory T cells from allergic patients, resulted in a decrease in IL-5 production compared to non-pulsed MD-DCs cultured in the presence of Der p 1. BCG, and especially rBCG-hIL-18, may thus be potential therapeutic tools to reduce exacerbated Th2 responses in patients with allergic asthma.
Highlights
IntroductionBacillus Calmette–Guérin (BCG), the only currently available vaccine against tuberculosis, has a number of beneficial off-target effects and is able to protect against various infectious and non-infectious diseases, including allergic asthma (for a review see [1])
In order to explore the immunomodulatory effects of Bacillus Calmette–Guérin (BCG) and rBCG-hIL-18 in a Der p 1-induced allergic environment, we used a well-established in vitro model of dendritic cells (DCs)-T cell cocultures, as professional antigen-presenting cells DCs play a key role in the initiation and development of allergic diseases
Allergy that in the presence of Der p 1, the IL-5 production by naïve T cells from allergic patients was significantly decreased by BCG and even more by rBCG-hIL-18
Summary
Bacillus Calmette–Guérin (BCG), the only currently available vaccine against tuberculosis, has a number of beneficial off-target effects and is able to protect against various infectious and non-infectious diseases, including allergic asthma (for a review see [1]). Asthma is one of the most common forms of allergic disease in industrialized countries, and approximately 300 million people are affected by it. It continues to be a significant health burden and a major cause of disability-adjusted life span in adults and children [2]. Allergic asthma is characterized by excessive production of. Th2-related cytokines by allergen-specific CD4+ T cells [3,4].
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