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      Host–microbe cross-talk in the lung microenvironment: implications for understanding and treating chronic lung disease

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          Abstract

          Chronic respiratory diseases are highly prevalent worldwide and will continue to rise in the foreseeable future. Despite intensive efforts over recent decades, the development of novel and effective therapeutic approaches has been slow. However, there is new and increasing evidence that communities of micro-organisms in our body, the human microbiome, are crucially involved in the development and progression of chronic respiratory diseases. Understanding the detailed mechanisms underlying this cross-talk between host and microbiota is critical for development of microbiome- or host-targeted therapeutics and prevention strategies. Here we review and discuss the most recent knowledge on the continuous reciprocal interaction between the host and microbes in health and respiratory disease. Furthermore, we highlight promising developments in microbiome-based therapies and discuss the need to employ more holistic approaches of restoring both the pulmonary niche and the microbial community.

          Abstract

          The reciprocal interaction between microbes and host in the lung is increasingly recognised as an important determinant of health. The complexity of this cross-talk needs to be taken into account when studying diseases and developing future new therapies. https://bit.ly/2VKYUfT

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          Most cited references105

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          An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system.

          The mammalian gastrointestinal tract harbors a complex ecosystem consisting of countless bacteria in homeostasis with the host immune system. Shaped by evolution, this partnership has potential for symbiotic benefit. However, the identities of bacterial molecules mediating symbiosis remain undefined. Here we show that, during colonization of animals with the ubiquitous gut microorganism Bacteroides fragilis, a bacterial polysaccharide (PSA) directs the cellular and physical maturation of the developing immune system. Comparison with germ-free animals reveals that the immunomodulatory activities of PSA during B. fragilis colonization include correcting systemic T cell deficiencies and T(H)1/T(H)2 imbalances and directing lymphoid organogenesis. A PSA mutant of B. fragilis does not restore these immunologic functions. PSA presented by intestinal dendritic cells activates CD4+ T cells and elicits appropriate cytokine production. These findings provide a molecular basis for host-bacterial symbiosis and reveal the archetypal molecule of commensal bacteria that mediates development of the host immune system.
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            Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus

            Rhinoviruses are the major trigger of acute asthma exacerbations and asthmatic subjects are more susceptible to these infections. To investigate the underlying mechanisms of this increased susceptibility, we examined virus replication and innate responses to rhinovirus (RV)-16 infection of primary bronchial epithelial cells from asthmatic and healthy control subjects. Viral RNA expression and late virus release into supernatant was increased 50- and 7-fold, respectively in asthmatic cells compared with healthy controls. Virus infection induced late cell lysis in asthmatic cells but not in normal cells. Examination of the early cellular response to infection revealed impairment of virus induced caspase 3/7 activity and of apoptotic responses in the asthmatic cultures. Inhibition of apoptosis in normal cultures resulted in enhanced viral yield, comparable to that seen in infected asthmatic cultures. Examination of early innate immune responses revealed profound impairment of virus-induced interferon-β mRNA expression in asthmatic cultures and they produced >2.5 times less interferon-β protein. In infected asthmatic cells, exogenous interferon-β induced apoptosis and reduced virus replication, demonstrating a causal link between deficient interferon-β, impaired apoptosis and increased virus replication. These data suggest a novel use for type I interferons in the treatment or prevention of virus-induced asthma exacerbations.
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              Role of deficient type III interferon-lambda production in asthma exacerbations.

              Rhinoviruses are the major cause of asthma exacerbations, and asthmatics have increased susceptibility to rhinovirus and risk of invasive bacterial infections. Here we show deficient induction of interferon-lambdas by rhinovirus in asthmatic primary bronchial epithelial cells and alveolar macrophages, which was highly correlated with severity of rhinovirus-induced asthma exacerbation and virus load in experimentally infected human volunteers. Induction by lipopolysaccharide in asthmatic macrophages was also deficient and correlated with exacerbation severity. These results identify previously unknown mechanisms of susceptibility to infection in asthma and suggest new approaches to prevention and/or treatment of asthma exacerbations.
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                Author and article information

                Journal
                Eur Respir J
                Eur. Respir. J
                ERJ
                erj
                The European Respiratory Journal
                European Respiratory Society
                0903-1936
                1399-3003
                August 2020
                20 August 2020
                : 56
                : 2
                : 1902320
                Affiliations
                [1 ]University of Groningen, Dept of Molecular Pharmacology, GRIAC Research Institute, Groningen, The Netherlands
                [2 ]Dept of Pulmonology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
                [3 ]Airways Disease, National Heart and Lung Institute, Imperial College London, London, UK
                [4 ]Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
                [5 ]Division of Pulmonary and Critical Care Medicine, Dept of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
                [6 ]Michigan Center for Integrative Research in Critical Care, Ann Arbor, MI, USA
                [7 ]Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and the University of Newcastle, Newcastle, Australia
                [8 ]Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, Sydney, Australia
                [9 ]Early Life Origins of Chronic Lung Disease, Research Center Borstel, Leibniz Lung Center, Airway Research Center North, Member of the German Center for Lung Research (DZL), Borstel, Germany
                [10 ]Institute for Experimental Medicine, Christian-Albrechts-Universitaet zu Kiel, Kiel, Germany
                [11 ]Dept of Parasitology, Leiden University Medical Center, Leiden, The Netherlands
                [12 ]Dept of Medical Microbiology, NUTRIM – School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
                [13 ]University of Groningen, University Medical Center Groningen, Dept of Pathology and Medical Biology, GRIAC Research Institute, Groningen, The Netherlands
                Author notes
                Sabine Bartel, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. E-mail: s.r.bartel@ 123456umcg.nl
                Author information
                https://orcid.org/0000-0002-0238-5982
                https://orcid.org/0000-0003-2101-8843
                https://orcid.org/0000-0001-9279-2890
                https://orcid.org/0000-0001-9279-2890
                https://orcid.org/0000-0002-9163-795X
                Article
                ERJ-02320-2019
                10.1183/13993003.02320-2019
                7439216
                32430415
                cf30ab42-bb18-4323-98b7-7968cfd24445
                Copyright ©ERS 2020

                This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

                History
                : 30 November 2018
                : 20 April 2020
                Funding
                Funded by: FP7 People: Marie-Curie Actions, open-funder-registry 10.13039/100011264;
                Award ID: 713406
                Funded by: Nederlandse Organisatie voor Wetenschappelijk Onderzoek, open-funder-registry 10.13039/501100003246;
                Award ID: 91714352
                Funded by: National Health and Medical Research Council, open-funder-registry 10.13039/501100000925;
                Award ID: 1059238
                Award ID: 1079187
                Funded by: Leibniz Competition 2016 (SKE)
                Award ID: The Lung Microbiota at the Interface between Airwa
                Funded by: Netherlands lung foundation
                Award ID: 12017001
                Award ID: 5115015
                Categories
                Back to Basics

                Respiratory medicine
                Respiratory medicine

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