Asthma: Researchers of the University of Liège discover how exposure to microbes protects against asthma and propose a cell therapy approach that can lead to novel treatments for the disease

The incidence of asthma is increasing steadily, especially in developed countries. One of the reasons given for this rise is the excessive level of hygiene in our environment. Epidemiological studies have indeed shown that exposure to a so-called "non-hygienic" environment, rich in microbes, plays a protective role against the development of allergies, including asthma. Conversely, a too hygienic environment would predispose to asthma, although the reasons are not known. In allergic reactions such as asthma, our immune system does not function properly and responds exaggeratedly to harmful allergens present in the environment (pollens, mites, etc.). In an article published in Immunity, researchers at the University of Liège show that exposure to bacterial DNA (one of the microbial compounds) drastically amplifies a population of pulmonary macrophages and makes them strongly immunosuppressive, which prevents and treats asthma in mice. This discovery offers promising prospects for the development of a cell therapy based on the administration of these regulatory macrophages to asthmatic patients.

Led by Professor Fabrice Bureau (Ordinary Professorand Welbio Investigator - Walloon Excellence in Life Sciences and Biotechnology) and Dr. Thomas Marichal (Research Associate of the F.R.S.-FNRS), both researchers at the GIGA-University of Liège, the scientific team has discovered how a non-hygienic environment, rich in bacterial DNA, helps to protect against asthma. Notably, synthetic compounds mimicking bacterial DNA have been tested in other studies in humans for their therapeutic effect in the treatment of asthma, but until now none of these compounds have been approved on the market. This may be due to their toxicity or the lack of basic knowledge about their mechanism of action. Here, on the one hand, the mechanisms of action have been identified, and on the other hand, this study would allow a cell therapy approach that would avoid the use of potentially toxic compounds.

In this study in mice, researchers first looked at how exposure to microbial compounds (such as bacterial wall components, or their own DNA), or whole microbes, would modify the immune environment of the lung. They found that bacterial DNA, unlike the other compounds, was able to strongly amplify a population of so-called interstitial macrophages and that this expansion persisted for several months in the individual.

Surprisingly, if these same macrophages were isolated from a mouse and re-injected into the lungs of a naive recipient mouse, such individual was not capable of developing asthma against house dust mite extracts. Similarly, if these macrophages were transferred to an asthmatic mouse, the asthmatic mouse was cured and no more symptoms of asthma were present. Based on these results, the researchers now envision "making" macrophages with similar properties in vitro from monocytes, a white blood cell type found in the human blood.

"If it is possible to create suppressive macrophage from blood monocytes of asthmatic patients, it is quite conceivable to reinject these macrophages into the lungs of these same patients, during routine bronchoscopy procedures performed by pneumologists here at the CHU Liège, and to evaluate the therapeutic potential of these cells", concludes Prof. Fabrice Bureau.

The researchers have just filed a patent to protect their results and invention, and are going to initiate studies in humans.

Full bibliographic information


"Bacterial CpG-DNA protects against asthma by expanding lung interstitial regulatory macrophages from local and splenic reservoir monocytes" Immunity.

Authors
Catherine Sabatel1,2,11, Coraline Radermecker1,2,11, Laurence Fievez1,11, Genevieve Paulissen1, Svetoslav Chakarov3, Claudia Fernandes1, Sabine Olivier1, Marie Toussaint4, Dimitri Pirottin1,2, Xue Xiao2,5, Pascale Quatresooz6, Jean-Claude Sirard7, Didier Cataldo8, Laurent Gillet2,5, Hicham Bouabe9, Christophe J. Desmet1, Florent Ginhoux3, Thomas Marichal1,2,12,* & Fabrice Bureau1,2,10,12,*

Affiliations
1Laboratory of Cellular and Molecular Immunology, GIGA-Research, University of Liège, Liège, Belgium
2Faculty of Veterinary Medicine, University of Liège, Liège, Belgium
3Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore
4Airway Disease Infection Section, National Heart and Lung Institute (NHLI), Imperial College London, London, UK
5Laboratory of Immunology-Vaccinology, Fundamental and Applied Research for Animals & Health, University of Liège, Liège, Belgium
6Department of Human Histology, CRPP, University of Liège, Liège, Belgium
7University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR 8204-CIIL-Center for Infection and Immunity of Lille, Lille, France
8Laboratory of Tumor and Developmental Biology, GIGA-Research, University of Liège, Liège, Belgium
9Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, UK
10WELBIO, Walloon Excellence in Life Sciences and Biotechnology, Wallonia, Belgium
11Co-first authors
12Lead contacts

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