Cytotoxic effects of halophilic archaea metabolites on ovarian cancer cell lines.

BACKGROUND: Ovarian cancer is one of the most frequent and deadly gynaecological cancers, often resistant to platinum-based chemotherapy, the current standard of care. Halophilic microorganisms have been shown to produce a large variety of metabolites, some of which show toxicity to various cancer cell lines. However, none have yet been shown to be active against ovarian cancer cells. Here, we examined the effects of metabolites secreted by the halophilic archaea Halorhabdus rudnickae and Natrinema salaciae on various cancer cell lines, including ovarian cancer cell lines. RESULTS: 1H NMR analyses of Hrd. rudnickae and Nnm. salaciae culture supernatants contain a complex mixture of metabolites that differ between species, and even between two different strains of the same species, such as Hrd. rudnickae strains 64T and 66. By using the MTT and the xCELLigence RTCA assays, we found that the secreted metabolites of all three halophilic strains expressed cytotoxicity to the ovarian cancer cell lines, especially A2780, as well as its cisplatin-resistant derivative A2780cis, in a dose-dependent manner. The other tested cell lines A549, HepG2, SK-OV-3 and HeLa were only minimally, or not at all affected by the archaeal metabolites, and this was only seen with the MTT assay. CONCLUSIONS: The halophilic archaea Hrd. rudnickae and Nnm. salaciae, isolated from a Polish salt mine and Lake Medee in the Mediterranean Sea, respectively, secrete metabolites that are active against ovarian cancer cells, including those that are resistant to cisplatin. This opens potential new possibilities for the treatment of these frequent and deadly gynaecological cancers.

Effect of Cyclophosphamide Treatment on Central and Effector Memory T Cells in Mice.

Immunological memory is a key feature of adaptive immunity. It provides the organism with long-lived and robust protection against infection. The important question is whether cyclophosphamide (CP), as immunosuppressive agent used in cancer therapy and in some autoimmune diseases, may act on the memory T-cell population. We investigated the effect of CP on the percentage of central memory T cells (TCM) and effector memory T cells (TEM) in the mouse model of CP-induced immunosuppression (8-10-week-old male C57BL/6 mice CP treated for 7 days at the daily dose of 50 µg/g body weight [bw], manifested the best immunosuppression status, as compared to lower doses of CP: 10 or 20 µg/g bw). The CP induced a significant decrease in the percentage of CD8+ (TCM), compared to nonimmunosuppressed mice. This effect was not observed in the case of CD4+ TCM population. The percentage of gated TEM with CD4 and CD8 phenotype was significantly decreased in CP-treated mice, as compared to the control ones. Taken together, the above data indicate that CP-induced immunosuppression in mice leads to a reduction in the abundance of central memory cells possessing preferentially CD8+ phenotype as well as to a reduction in the percentage of effector memory cells (splenocytes both CD4+ and CD8+), compared to the cells from nonimmunosuppressed mice. These findings in mice described in this article may contribute to the understanding of the complexity of the immunological responses in humans and extend research on the impact of the CP model of immunosuppression in mice and memory T-cell populations.

[Immunosuppression - tough ally in torrid time]. / Immunosupresja ­ wymagajacy sprzymierzeniec na trudne czasy.

Immunosuppression is a condition characterized by weakened or inhibited immune response. It occurred both in humoral and cellular response. This is related to the variable levels of deficiency for each antibody class (IgG, IgM, IgA) and a decrease in the number and function of immune cells, mainly T cells which results in the inhibition of cytokine production, signaling transduction and clonal expansion. Immunosuppressive therapy is used in many fields of medicine, such as transplantology, oncology, autoimmune disorders. Immunosuppression can be induced in several ways, by the surgical resection of the organs of the immune system, physical methods using X-rays or chemical methods using pharmacological agents. The most common way to induce immunosuppression is the administration of immunosuppressive drugs, amongst others: glucocorticoids, cytostatic drugs, immunophilin-binding agents, monoclonal antibodies. Unfortunately, the desired therapeutic effects of immunosuppression may be accompanied by a number of side effects associated with both impaired immunity (susceptibility to infections, including those caused by opportunistic microorganisms), toxic effects on the tissues (nephrotoxicity, neurotoxicity), or with a direct impact on the processes of malignancy. This harmful influence can be limited by the modification of the existing drugs, looking for new ones or developing new methods for the controlled kinetics of releasing the immunosuppressive pharmaceuticals. The personalization of immunosuppressant treatment according to genetic/genomic characteristics of individual patient represents the quite innovative look into the issue of immunosuppression.

Monocyte signal transduction receptors in active and latent tuberculosis.

The mechanisms that promote either resistance or susceptibility to TB disease remain insufficiently understood. Our aim was to compare the expression of cell signaling transduction receptors, CD14, TLR2, CD206, and ß2 integrin LFA-1 on monocytes from patients with active TB or nonmycobacterial lung disease and healthy individuals with M.tb latency and uninfected controls to explain the background of the differences between clinical and subclinical forms of M.tb infection. A simultaneous increase in the expression of the membrane bound mCD14 receptor and LFA-1 integrin in patients with active TB may be considered a prodrome of breaking immune control by M.tb bacilli in subjects with the latent TB and absence of clinical symptoms.

Interaction of Helicobacter pylori with C-type lectin dendritic cell-specific ICAM grabbing nonintegrin.

In this study we asked whether Helicobacter pylori whole cells and lipopolysaccharide (LPS) utilize sugar moieties of Lewis (Le) antigenic determinants to interact with DC-SIGN (dendritic cell specific ICAM grabbing nonintegrin) receptor on dendritic cells (DCs). For this purpose the soluble DC-SIGN/Fc adhesion assay and the THP-1 leukemia cells with induced expression of DC-SIGN were used. We showed that the binding specificity of DC-SIGN with H. pylori Le(X/Y) positive whole cells and H. pylori LPS of Le(X/Y) type was fucose dependent, whereas in Le(XY) negative H. pylori strains and LPS preparations without Lewis determinants, this binding was galactose dependent. The binding of soluble synthetic Le(X) and Le(Y) to the DC-SIGN-like receptor on THP-1 cells was also observed. In conclusion, the Le(XY) dependent as well as independent binding of H. pylori whole cells and H. pylori LPS to DC-SIGN was described. Moreover, we demonstrated that THP-1 cells may serve as an in vitro model for the assessment of H. pylori-DC-SIGN interactions mediated by Le(X) and Le(Y) determinants.

Latent M. tuberculosis infection--pathogenesis, diagnosis, treatment and prevention strategies.

One third of the earths population is infected with Mycobacterium tuberculosis (Mtb), but only 5-10% of the infected individuals develop active tuberculosis (TB) over their lifetime. The remaining 90-95% stay healthy and are called latently infected individuals. They are the biggest reservoir of the tubercle bacilli and identifying the cases of latent TB is a part of the global plan of TB control. From the clinical point of view detection of latent TB infections (LTBI) in individuals with the highest active TB risk including cases of HIV infection, autoimmune inflammatory diseases or cancer, is a priority. This review summarizes the recent findings in the pathogenesis of latent TB, its diagnosis, treatment and prevention.

Recombinant BCG to Enhance Its Immunomodulatory Activities.

The bacillus Calmette-Guérin (BCG) is an attenuated Mycobacterium bovis derivative that has been widely used as a live vaccine against tuberculosis for a century. In addition to its use as a tuberculosis vaccine, BCG has also been found to have utility in the prevention or treatment of unrelated diseases, including cancer. However, the protective and therapeutic efficacy of BCG against tuberculosis and other diseases is not perfect. For three decades, it has been possible to genetically modify BCG in an attempt to improve its efficacy. Various immune-modulatory molecules have been produced in recombinant BCG strains and tested for protection against tuberculosis or treatment of several cancers or inflammatory diseases. These molecules include cytokines, bacterial toxins or toxin fragments, as well as other protein and non-protein immune-modulatory molecules. The deletion of genes responsible for the immune-suppressive properties of BCG has also been explored for their effect on BCG-induced innate and adaptive immune responses. Most studies limited their investigations to the description of T cell immune responses that were modified by the genetic modifications of BCG. Some studies also reported improved protection by recombinant BCG against tuberculosis or enhanced therapeutic efficacy against various cancer forms or allergies. However, so far, these investigations have been limited to mouse models, and the prophylactic or therapeutic potential of recombinant BCG strains has not yet been illustrated in other species, including humans, with the exception of a genetically modified BCG strain that is now in late-stage clinical development as a vaccine against tuberculosis. In this review, we provide an overview of the different molecular engineering strategies adopted over the last three decades in order to enhance the immune-modulatory potential of BCG.

Halophilic Archaea Halorhabdus Rudnickae and Natrinema Salaciae Activate Human Dendritic Cells and Orient T Helper Cell Responses.

Halophilic archaea are procaryotic organisms distinct from bacteria, known to thrive in hypersaline environments, including salt lakes, salterns, brines and salty food. They have also been identified in the human microbiome. The biological significance of halophiles for human health has rarely been examined. The interactions between halophilic archaea and human dendritic cells (DCs) and T cells have not been identified so far. Here, we show for the first time that the halophilic archaea Halorhabdus rudnickae and Natrinema salaciae activate human monocyte-derived DCs, induce DC maturation, cytokine production and autologous T cell activation. In vitro both strains induced DC up-regulation of the cell-surface receptors CD86, CD80 and CD83, and cytokine production, including IL-12p40, IL-10 and TNF-α, but not IL-23 and IL-12p70. Furthermore, autologous CD4+ T cells produced significantly higher amounts of IFN-γ and IL-13, but not IL-17A when co-cultured with halophile-stimulated DCs in comparison to T cells co-cultured with unstimulated DCs. IFN-γ was almost exclusively produced by naïve T cells, while IL-13 was produced by both naïve and memory CD4+ T cells. Our findings thus show that halophilic archaea are recognized by human DCs and are able to induce a balanced cytokine response. The immunomodulatory functions of halophilic archaea and their potential ability to re-establish the immune balance may perhaps participate in the beneficial effects of halotherapies.

Mycobacterium bovis Wild-Type BCG or Recombinant BCG Secreting Murine IL-18 (rBCG/IL-18) Strains in Driving Immune Responses in Immunocompetent or Immunosuppressed Mice.

Mycobacterium tuberculosis infections remain a global health problem in immunosuppressed patients. The effectiveness of BCG (Bacillus Calmette−Guérin), an anti-tuberculosis vaccine, is unsatisfactory. Finding a new vaccine candidate is a priority. We compared numerous immune markers in BCG-susceptible C57BL/6 and BCG-resistant C3H mice who had been injected with 0.9% NaCl (control) or with wild-type BCG or recombinant BCG secreting interleukin (IL)-18 (rBCG/IL-18) and in immunized mice who were immunocompromised with cyclophosphamide (CTX). The inoculation of rBCG/IL-18 in immunocompetent mice increased the percentage of bone marrow myeloblasts and promyelocytes, which were further elevated in the rBCG/IL-18/CTX-treated mice: C57BL/6 mice­3.0% and 11.4% (control) vs. 18.6% and 42.4%, respectively; C3H mice­1.1% and 7.7% (control) vs. 18.4% and 44.9%, respectively, p < 0.05. The bone marrow cells showed an increased mean fluorescence index (MFI) in the CD34 adhesion molecules: C57BL/6 mice­4.0 × 103 (control) vs. 6.2 × 103; C3H mice­4.0 × 103 (control) vs. 8.0 × 103, p < 0.05. Even in the CTX-treated mice, the rBCG/IL-18 mobilized macrophages for phagocytosis, C57BL/6 mice­4% (control) vs. 8%; C3H mice­2% (control) vs. 6%, and in immunocompetent mice, C57BL/6 induced the spleen homing of effector memory CD4+ and CD8+ T cells (TEM), 15% (control) vs. 28% and 8% (control) vs. 22%, respectively, p < 0.05. In conclusion, rBCG/IL-18 effectively induced selected immune determinants that were maintained even in immunocompromised mice.

Premature chromosome condensation induced by caffeine, 2-aminopurine, staurosporine and sodium metavanadate in S-phase arrested HeLa cells is associated with a decrease in Chk1 phosphorylation, formation of phospho-H2AX and minor cytoskeletal rearrangements.

Here, we demonstrate that in HeLa cells, Ser317 of Chk1 undergoes phosphorylation in response to replication stress induced by hydroxyurea. We also demonstrate the existence of constitutive (interphase and mitotic) Chk1 kinase phosphorylation, the translocation of its phosphorylated form from the nucleus to cytoplasm in prometaphase as well as strong labeling of apoptotic nuclei with α-Chk1(S317) antibodies. Additionally, we show that caffeine, 2-aminopurine, staurosporine and sodium metavanadate can induce premature chromosome condensation (PCC) by the abrogation of the S-M checkpoint. Staurosporine appeared to be the most effective PCC inductor, and as in the case of the remaining inductors, the addition of hydroxyurea each time brought about an increase in the number of cells showing PCC symptoms (synergic effect). The forced premature mitosis was accompanied by an increasing index of double-strand breaks marked by the phosphorylation of histone H2AX on Ser139. Moreover, we found that the chemicals used brought about minor actin and tubulin network rearrangements that occurred following either replication stress or drug-induced cell cycle delay. At the same time, it was found that the extent of the cytoskeleton rearrangement did not hinder PCC in all its subperiods, i.e., from PCC-type prophase to PCC-type telophase.

[Nontuberculous mycobacteria: M. marinum, M. ulcerans, M. xenopi - brief characteristics of the bacteria and diseases caused by them]. / Pratki niegruzlicze: M. marinum, M. ulcerans, M. xenopi ­ krótka charakterystyka drobnoustrojów i zmian klinicznych przez nie wywolywanych.

Mycobacterium is a variable group of acid-fast bacillus which contains pathogenic bacteria causing tuberculosis (MTC - Mycobacterium tuberculosis complex) and leprosy (M. leprae) as well as numerous nontuberculous mycobacteria (NTM) causing diseases mostly in people with immunodeficiency, although some NTM strains are capable of causing illnesses in non-immunocompromised patients. This group includes for example Mycobacterium marinum, Mycobacterium ulcerans and Mycobacterium xenopi. These microorganisms are environmental mycobacteria, present in developing countries of Africa, but they may also be transferred to other continents. The most common symptoms of diseases caused by these species are skin lesions (hyperpigmentation, tumors, ulcers) and arthritis. Because of the rarity of their occurrence, these mycobacteria are relatively poorly known. Effective ways of treating the diseases caused by these bacilli are still under study.

[Vaccination against M. tuberculosis - what next after BCG?]. / Szczepienia przeciwpratkowe ­ BCG i co dalej?

Tuberculosis (TB) still remains a huge global health problem. An increase in TB has been observed in many parts of the world, especially in poor and densely populated sub-Saharan Africa and Asia. Tuberculosis affects not only the developing countries but also the relatively wealthy regions of Europe, particularly Eastern Europe, where drug-resistant mycobacterial strains are increasingly reported. Control of tuberculosis expansion is very difficult. It requires the long-term use of anti-mycobacterial drugs. Additionally, the HIV epidemic and the phenomenon of multi-drug resistance are assumed to be responsible for the increase in TB cases. Therefore the most reasonable form of anti-TB protection seems to be effective vaccination. At the beginning of the twentieth century the BCG vaccine was introduced into general use as the first and so far the only immune protector against tuberculosis. Now it is known that this vaccine is not powerful enough and induces protection at a relatively low level. Hence ongoing research on the development of a more powerful anti-mycobacterial vaccine is still needed. Many of the new formulations are in phase II or III of clinical trials and the results are promising. The search for new vaccines involves several strategies: modified virulence-attenuated Mycobacterium tuberculosis strains, recombination of attenuated M. bovis BCG bacilli, immunogenic mycobacterial proteins and DNA encoding selected proteins as well as unrelated microorganisms used as carriers of mycobacterial antigens. The wide range of concepts is extremely important because new vaccines should serve for immunization of the broadest possible population, not only healthy individuals but also those who are immunocompromised.

BCG for the prevention and treatment of allergic asthma.

Allergic diseases, in particular atopic asthma, have been on the rise in most industrialized countries for several decades now. Allergic asthma is characterized by airway narrowing, bronchial hyperresponsiveness, excessive airway mucus production, eosinophil influx in the lungs and an imbalance of the Th1/Th2 responses, including elevated IgE levels. Most available interventions provide only short-term relief from disease symptoms and do not alter the underlying immune imbalance. A number of studies, mostly in mouse models, have shown that Mycobacterium bovis bacillus Calmette-Guérin (BCG) treatment is capable of preventing or reducing an established allergen-driven inflammatory response, by redirecting pathogenic Th2 towards protective Th1 and/or regulatory T cell responses. Dendritic cells stimulated by BCG appear to be a crucial first step in the immunomodulatory effects of BCG. While the protective and therapeutic effects of BCG against allergy and asthma are well documented in animal models, they are less clear in humans, both in observational studies and in randomized controlled trials. The purpose of this article is to provide an up-to-date overview of the available evidence on the anti-allergy, in particular anti-asthma effects of BCG in mice, rats and humans.

Archaeosomes and Gas Vesicles as Tools for Vaccine Development.

Archaea are prokaryotic organisms that were classified as a new domain in 1990. Archaeal cellular components and metabolites have found various applications in the pharmaceutical industry. Some archaeal lipids can be used to produce archaeosomes, a new family of liposomes that exhibit high stability to temperatures, pH and oxidative conditions. Additionally, archaeosomes can be efficient antigen carriers and adjuvants promoting humoral and cellular immune responses. Some archaea produce gas vesicles, which are nanoparticles released by the archaea that increase the buoyancy of the cells and facilitate an upward flotation in water columns. Purified gas vesicles display a great potential for bioengineering, due to their high stability, immunostimulatory properties and uptake across cell membranes. Both archaeosomes and archaeal gas vesicles are attractive tools for the development of novel drug and vaccine carriers to control various diseases. In this review we discuss the current knowledge on production, preparation methods and potential applications of archaeosomes and gas vesicles as carriers for vaccines. We give an overview of the traditional structures of these carriers and their modifications. A comparative analysis of both vaccine delivery systems, including their advantages and limitations of their use, is provided. Gas vesicle- and archaeosome-based vaccines may be powerful next-generation tools for the prevention and treatment of a wide variety of infectious and non-infectious diseases.

Decrease of IL-5 Production by Naive T Cells Cocultured with IL-18-Producing BCG-Pulsed Dendritic Cells from Patients Allergic to House Dust Mite.

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.

Anti-neoplastic effect of protein kinase CK2 inhibitor, 2-dimethylamino-4,5,6,7-tetrabromobenzimidazole (DMAT), on growth and hormonal activity of human adrenocortical carcinoma cell line (H295R) in vitro.

Several studies indicate the involvement of protein kinases in the progression of various malignancies. Kinase inhibitors are therefore becoming important anticancer drugs. CK2 kinase (casein kinase-2) has been suggested to be a constituent of a neoplastic milleu, and its inhibition might represent a new approach to cancer therapy. Adrenocortical carcinomas (ACCs) are highly malignant neoplasms with poor overall prognosis. We have examined the effects of 2-dimethylamino-4,5,6,7-tetrabromobenzimidazole (DMAT), a potent CK2 inhibitor, on the H295R human adrenocortical cancer cell line. Treatment with DMAT decreases the secretion of aldosterone, dehydroepiandrosterone sulfate, and androstendione and results in an accumulation of 17-OH-progesterone. Cell growth as measured by the MTT and 5-bromo-2'-deoxyuridine incorporation assays is inhibited, and cell cycle analysis has revealed a slight induction of apoptosis. Thus, CK2 kinase activity is probably involved in human ACC endocrine activity and growth.

Tuberculin skin test reaction is related to memory, but not naive CD4+ T cell responses to mycobacterial stimuli in BCG-vaccinated young adults.

Bacillus Calmette-Guérin (BCG) is the only vaccine available against tuberculosis and the tuberculin skin test (TST) is the most widely used method to detect BCG take. However, subjects may remain TST-negative, even after several BCG administrations. To investigate some of the potential reasons underlying this inability of developing tuberculin sensitivity in response to BCG we compared the effect of different mycobacterial stimuli in the groups differently responding to tuberculin. TST was performed on 71 healthy adults aged 25-30 years, who had received BCG in their childhood, and considered TST-positive at ≥10 mm. Dendritic cells (DCs) were incubated with PPD, live BCG or rBCGhIL-18, producing human IL-18. The latter strain was used to investigate whether the production of IL-18 could overcome some of the immune read-out limitations in the TST-negative subjects. CD86, CD80, CD40, and DC-specific intracellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) expression was analysed by flow cytometry and IL-10, IL-23 and IP-10 secretion in culture supernatants by ELISA. In DCs-T cell co-cultures with naive and memory CD4+ T cells, the IFN-γ and IL-10 levels were determined by ELISA. We found no difference in IL-10 and IFN-γ production by naive T cells between the TST-negative and TST-positive subjects. However, IFN-γ was produced in significantly higher amounts by memory T cells incubated with PPD, BCG or rBCGhIL-18-pulsed DCs in TST-positive than in TST-negative subjects, whereas the numbers of the IFN-γ-producing T cells were similar in both groups. This difference may be partially due to a decreased CD40 and enhanced reduction in DC-SIGN expression by DCs of TST-negative versus TST-positive subjects. A strong effect of IL-18 expression by rBCGhIL-18 on IL-23 production by the DC was seen in both groups, which likely was the reason for the increased IFN-γ production by naïve T cells upon incubation with mycobacteria-pulsed DC, regardless of the TST status.

BCG and protection against inflammatory and auto-immune diseases.

INTRODUCTION: Bacillus Calmette-Guérin (BCG) is the only available vaccine against tuberculosis. Although its protective efficacy against pulmonary tuberculosis is still under debate, it provides protection against other mycobacterial diseases. BCG is also an effective therapy against superficial bladder cancer and potentially decreases overall childhood mortality. Areas covered: The purpose of this paper is to provide a state-of-the-art summary of the beneficial effects of BCG in inflammatory and auto-immune diseases. As a strong inducer of Th1 type immunity, BCG has been reported to protect against atopic conditions, such as allergic asthma, a Th2-driven disorder. Its protective effect has been well documented in mice, but still awaits definitive evidence in humans. Similarly, murine studies have shown a protective effect of BCG against auto-immune diseases, such as multiple sclerosis and insulin-dependent diabetes, but studies in humans have come to conflicting conclusions. Expert commentary: Studies in mice have shown a beneficial effect of the BCG vaccine against allergic asthma, multiple sclerosis and diabetes. However, the understanding of its mechanism is still fragmentary and requires further in depth research. Some observational or intervention studies in humans have also suggested a beneficial effect, but definitive evidence for this requires confirmation in carefully conducted prospective studies.

Tuberculosis bacilli still posing a threat. Polymorphism of genes regulating anti-mycobacterial properties of macrophages.

One third of the earth's population is infected with Mycobacterium tuberculosis, but only 5-10% of the infected individuals will develop active disease over their lifetime. To identify the genes responsible for the variation in the human susceptibility/resistance to tuberculosis (TB) we determined the polymorphisms of three genes crucial for the function of macrophages, in TB patients and healthy controls with no past history of TB. We found no association between the polymorphisms of the NRAMP-INT4, MBL (codons 52, 54, 57) and CD14-159 genes and TB in a Caucasian Polish population. However, we have suggested a possible involvement of CD14 and MBL molecules in the host-mycobacteria interactions on the basis of the significant increase in the serum CD14 and MBL in TB patients compared to healthy controls.

Mycobacterium bovis BCG mycobacteria--new application.

The polarized response of T helper-2 (Th2) lymphocytes to an allergen is considered to be the main cause of the pathogenesis of asthma. In this study, we asked a question whether M. bovis BCG mycobacteria which are known for the preferential stimulation of T helper-1 (Th1) immunity, diminish the effector functions of Th2 cells from allergic patients upon stimulation with a common house dust mite Der p-1 allergen. Our results allow a positive answer to this question. We demonstrate that BCG modulates the dendritic cell-dependent allergen presentation process and switches naive T lymphocytes towards an anti-allergic Th1 profile.