Professor Jürgen Schwarze
Jürgen Schwarze's group studies immune mechanisms of viral bronchiolitis and the role of virus induced immune modulation in allergy and asthma focusing on the innate/adaptive immune interface in the lung.
- Matthew Burgess - Postdoc
- Piotr Janas - PhD Student
Infection with human respiratory syncytial virus (RSV) is the leading cause of viral bronchiolitis in infants and young children, accounting for ~70% of cases. RSV-bronchiolitis is associated with intense inflammation of the terminal airways and impairment of lung function, resulting in severe disease that requires hospital admission in about 3% of all infants. Globally, it is estimated that RSV is responsible for 33 million cases every year, 3 million hospitalisations and 120,000 deaths in children under 5 years of age. In addition, in the elderly, RSV results in considerable morbidity and mortality, similar to non-pandemic influenza. Furthermore, RSV bronchiolitis in infants is associated with an increased risk of subsequent recurrent wheeze, childhood asthma, and early sensitisation to allergens. Thus, RSV infections constitute a major health and economic burden. Despite this there is still neither a vaccine available nor do we have any specific treatment for RSV-bronchiolitis that would shorten the disease or reduce its severity.
- Smyth, R.L. & Openshaw, P.J. Bronchiolitis. Lancet 368, 312-322 (2006).
- Tregoning, J.S. & Schwarze, J. Respiratory viral infections in infants: causes, clinical symptoms, virology, and immunology. Clinical microbiology reviews 23, 74-98 (2010).
- Shi T. Et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet 390, 946-958 (2017).
- Falsey, A.R., Hennessey, P.A., Formica, M.A., Cox, C. & Walsh, E.E. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med 352, 1749-1759 (2005).
- Sigurs N. et al. Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life. Thorax, 1045-52 (2010).
Driven by the lack of disease modifying therapy for severe RSV disease and inspired by findings of an increased risk of asthma development and allergic sensitisation following RSV bronchiolitis in infants, my research since 1994 has focused on understanding virus-induced immune-modulation and inflammation in the lung.
Lung dendritic cells in respiratory viral infection and immune pathways to reactive airway disease
Dendritic cells as professional antigen presenting cells are essential for antigen-specific activation of T-cells and determine the quality of T-cell responses. In healthy lungs mature dendritic cells are rare and the immune environment is tolerogenic. Following RSV infection, we have demonstrated marked increases in numbers of mature pulmonary dendritic cells with increased antigen-presenting capacity. These increases occur with the advent of virus induced inflammation, when antiviral immune responses have already been triggered, and are still evident when the infection has resolved. Using both pre-clinical models and clinical samples, we currently investigate the role of these mature lung dendritic cells for the course of RSV induced inflammation and lung function changes, as well as for subsequent immune responses. Characterising subsets of myeloid and plasmacytoid dendritic cells in the lung by analysing their co-stimulatory molecules, cytokines and function, we aim to determine if virus induced lung dendritic cells are involved in modulating pulmonary immune responses and to elucidate their role in maintenance or resolution of RSV induced inflammation, in the development of T-cell memory to RSV antigens and in enhanced responses to allergens following RSV infection.
To understand the pathological mechanisms leading to recurrent preschool wheeze and childhood asthma more widely, we are part of the Breathing Together Study, a Wellcome Trust funded neonatal cohort study which seeks to identify epithelial cell mechanisms, immune pathways and microbiome influences in asthma development.
Lung dendritic cells in viral/bacterial co-infections
Investigating the origin of mature DCs after RSV infection we have previously found that they are primarily derived from local precursors in the lung, which are depleted in the process, resulting in a prolonged inability to mount a normal DCs response to a secondary stimulus. This may have major implications for the defence against secondary respiratory infections in particular with bacteria. Studies investigating the role of lung DCs in the interaction between concomitant and serial infections are currently being developed.
Lung epithelial cells as immune regulators
We have previously found that, in analogy to gut epithelial cells, lung epithelial cells can completely inhibit antigen-specific T cell proliferation and that this inhibition is lost when epithelial cells are infected with RSV. In a collaboration with Professors A. van Osterhout and I. Heijink (Groningen, NL) we also demonstrated a lower inhibitory capacity of lung epithelial cells in people with asthma. We now work to understand the inhibitory mechanisms involved and the effects of viral infection on these.
Lung epithelial cell 'memory'
Lung epithelial cells are known to contribute to antiviral and inflammatory responses. We currently explore if lung epithelial cells, in analogy to trained immunity of innate immune cells, are trained by stimuli such as viral and bacterial respiratory infection to respond differently to subsequent infection, e.g. with increased antiviral and decreased inflammatory responses.
Immune modulation to reduce RSV disease and inflammation
There is no effective treatment that would prevent or shorten severe RSV disease or reduce its intensity. In collaboration with Professors R. Maizels (Glasgow) and B. Marsland (Lausanne, Monash) and Dr H McSorley (CIR) we have recently shown in a pre-clinical model that a strictly enteric helminth infection, dependent on the presence of microbiota and mediated by type I interferon induction, can reduce viral titres and severity of a subsequent RSV infection of the lung. We currently investigate the underlying mechanisms of this ‘gut-lung-axis’ effect.
In addition, we collaborate with Dr D. Davidson (CIR) to study the ability of anti-microbial peptides to reduce RSV infection and subsequent disease.
Additional areas of research
In collaboration with Prof A. Sheikh (Edinburgh) applied clinical research in allergy, asthma and respiratory infections through the Asthma UK Centre for Applied Research and the National Institute for Health Research (NIHR) RESPIRE unit.
Professor Schwarze (FRCPCH) is the Edward Clark Chair of Child Life and Health at the University of Edinburgh, a paediatrician specialised in allergy and respiratory medicine, and an internationally recognised expert in immune mechanisms of RSV bronchiolitis and associated airway allergy.
Dr Schwarze qualified in Medicine from Freiburg University, Germany in 1988, trained as a paediatrician specialising in paediatric respiratory medicine and paediatric allergy and he now leads the paediatric allergy service at the Royal Hospital for Sick Children Edinburgh and has been the clinical lead for the national Children's and Young People's Allergy Network Scotland (2011 -2019).
In 1994, as a post-doctoral fellow at National Jewish Medical and Research Centre in Denver, Colorado, Dr Schwarze started to work on immune responses in RSV bronchiolitis and allergic airway disease. He continued his research at the Ruhr-University Bochum, Germany, and from 2002 to 2007 at Imperial College London where, as a Wellcome Trust Senior Fellow, he focused his research on the role of lung dendritic cells in respiratory viral infections and subsequent reactive airway disease. In 2007 he moved to the Centre for Inflammation Research at the University of Edinburgh and took up his current Chair in 2008.
Professor Schwarze's research programme aims to understand mechanisms of inflammation at the interface of innate and adaptive immunity in respiratory viral infections to help develop urgently required treatments for viral bronchiolitis in infants and virus driven asthma exacerbations. He uses both pre-clinical models and clinical samples to investigate the roles of lung dendritic cells and airway epithelial cells in the induction, maintenance and resolution of virus induced immune responses and inflammation in the lung.
Honours and Awards
- 1997 1st Prize von Pirquet Award by the American College of Allergy, Asthma and Immunology
- 1999 Johannes -Wenner-Preis (international award) from Society for Pediatric Pulmonary Medicine (GPP, Germany, Austria, Switzerland)
- 1999 Pulmedica-Preis (national award) from the Society for Lung and Respiration Research, German Society for Pneumology
- 2019 Jack Pepys Lecture, British Society for Allergy & Clinical Immunology
- Philippson K, Medical Doctorate, Bochum University (2003)
- Dr Marc Beyer, Post-doc (2001-2004)
- Peters N, PhD Thesis, Imperial College London (2006)
- Lee D C, PhD Thesis, Imperial College London (2008)
- Wythe S, PhD Thesis, Imperial College London (2009)
- Pribul P, PhD Thesis, Imperial College London (2009)
- Dr Hongwei Wang, Post-doc (2004-2009)
- Dr MacKenzie K, PhD Thesis, University of Edinburgh (2014)
- McFarlane A, PhD Thesis, University of Edinburgh (2014)
- Dr Amanda McFarlane, Post-doc (2014-2017)
- Dr Aoife Kerring, Post-doc (2012-2015)
- Honorary Consultant Paediatrician (NHS Lothian)
- Scottish Lead for NHS-NRS Children’s Research
- Chair of Jennifer Brown Research Laboratory Management Board
- Chair Section if Clinical & Basic Immunology (2017-19), European Academy of Allergy and Clinical Immunology
- Dr Henry McSorley
- Dr Donald Davidson
- Dr Chengcan Yao
- Dr Amy Buck
- Dr Richard Weller
- Professor Jürgen Haas
- Professor Aziz Sheikh
- Professor Ultan Power (Belfast)
- Professor Irene Heijink (Groningen)
- Professor Rick Maizels (Glasgow)
- Professor Peter Ghazal (Cardiff)
- The Breathing Together Investigators