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      Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma

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          Abstract

          Background

          Asthma is estimated to affect as many as 300 million people worldwide and its incidence and prevalence are rapidly increasing throughout the world, especially in children and within developing countries. Recently, there has been a growing interest in the use of potentially beneficial bacteria for allergic diseases. This study is aimed at exploring the therapeutic effects of long-term treatment with two different beneficial bacterial strains ( Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1) and a glucocorticoid (budesonide), as a reference treatment, on inflammatory response in a murine model for chronic allergic asthma.

          Methods

          To mimic the chronic disease in asthmatic patients, we used the murine ovalbumin-induced asthma model combined with prolonged allergen exposure. Airway function; pulmonary airway inflammation; airway remodelling, mRNA expression of pattern recognition receptors, Th-specific cytokines and transcription factors in lung tissue; mast cell degranulation; in vitro T cell activation; and expression of Foxp3 in blood Th cells were examined.

          Results

          Lactobacillus rhamnosus reduced lung resistance to a similar extent as budesonide treatment in chronically asthmatic mice. Pulmonary airway inflammation, mast cell degranulation, T cell activation and airway remodelling were suppressed by all treatments. Beneficial bacteria and budesonide differentially modulated the expression of toll-like receptors (TLRs), nod-like receptors (NLRs), cytokines and T cell transcription factors. Bifidobacterium breve induced regulatory T cell responses in the airways by increasing Il10 and Foxp3 transcription in lung tissue as well as systemic by augmenting the mean fluorescence intensity of Foxp3 in blood CD4+ T cells.

          Conclusion

          These findings show that Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1 have strong anti-inflammatory properties that are comparable to budesonide and therefore may be beneficial in the treatment of chronic asthma.

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          Most cited references50

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          Toll-like receptor 2 controls expansion and function of regulatory T cells.

          Tregs play a central role in the suppression of immune reactions and prevention of autoimmune responses harmful to the host. During acute infection, however, Tregs might hinder effector T cell activity directed toward the elimination of the pathogenic challenge. Pathogen recognition receptors from the TLR family expressed by innate immune cells are crucial for the generation of effective immunity. We have recently shown the CD4CD25 Treg subset in TLR2 mice to be significantly reduced in number compared with WT littermate control mice, indicating a link between Tregs and TLR2. Here, we report that the TLR2 ligand Pam3Cys, but not LPS (TLR4) or CpG (TLR9), directly acts on purified Tregs in a MyD88-dependent fashion. Moreover, when combined with TCR stimulation, TLR2 triggering augmented Treg proliferation in vitro and in vivo and resulted in a temporal loss of the suppressive Treg phenotype in vitro by directly affecting Tregs. Importantly, WT Tregs adoptively transferred into TLR2 mice were neutralized by systemic administration of TLR2 ligand during the acute phase of a Candida albicans infection, resulting in a 100-fold reduced C. albicans outgrowth. This demonstrates that in vivo TLR2 also controls the function of Tregs and establishes a direct link between TLRs and the control of immune responses through Tregs.
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            The cytokine network in chronic obstructive pulmonary disease.

            Multiple cytokines play a role in the orchestration of inflammation in inflammatory airway diseases, such as chronic obstructive pulmonary disease, through the recruitment, activation and survival of inflammatory cells. Lymphokines secreted from T cells regulate the pattern of inflammation, whereas proinflammatory cytokines amplify and perpetuate the inflammatory response. Multiple chemokines recruit inflammatory cells from the circulation into the lungs and many growth factors maintain this inflammation and lead to characteristic structural changes in the airways. There are several therapeutic approaches that target cytokine-mediated inflammation in chronic obstructive pulmonary disease, but blocking specific cytokines may not provide clinical benefit, whereas broad-spectrum anti-inflammatory approaches are more likely to be clinically effective.
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              Mouse models of allergic asthma: acute and chronic allergen challenge.

              Asthma is defined as a chronic inflammatory disease of the airways; however, the underlying physiological and immunological processes are not fully understood. Animal models have been used to elucidate asthma pathophysiology, and to identify and evaluate novel therapeutic targets. Several recent review articles (Epstein, 2004; Lloyd, 2007; Boyce and Austen, 2005; Zosky and Sly, 2007) have discussed the potential value of these models. Allergen challenge models reproduce many features of clinical asthma and have been widely used by investigators; however, the majority involve acute allergen challenge procedures. It is recognised that asthma is a chronic inflammatory disease resulting from continued or intermittent allergen exposure, usually via inhalation, and there has been a recent focus on developing chronic allergen exposure models, predominantly in mice. Here, we review the acute and chronic exposure mouse models, and consider their potential role and impact in the field of asthma research.
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                Author and article information

                Contributors
                Journal
                Respir Res
                Respir. Res
                Respiratory Research
                BioMed Central
                1465-9921
                1465-993X
                2014
                16 April 2014
                : 15
                : 1
                : 46
                Affiliations
                [1 ]Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, PO box 80082, 3508 TB Utrecht, The Netherlands
                [2 ]Danone Research, Centre for Specialised Nutrition, Wageningen, The Netherlands
                [3 ]Bioceros B.V., Utrecht, The Netherlands
                Article
                1465-9921-15-46
                10.1186/1465-9921-15-46
                4029990
                24735374
                6f7f3c2f-7f49-4ca0-ad83-bc03a0c7f6bf
                Copyright © 2014 Sagar et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                History
                : 9 June 2013
                : 3 April 2014
                Categories
                Research

                Respiratory medicine
                allergic asthma,beneficial bacteria,glucocorticoids,regulatory t cell
                Respiratory medicine
                allergic asthma, beneficial bacteria, glucocorticoids, regulatory t cell

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