According to the great paradigms of immunology, asthma, an allergic disease of the respiratory system, should always develop upon exposure to airborne antigens that are constantly being inhaled. However, the fact that 94 % of the Western population does not develop the disease suggests that as yet undefined mechanisms protect the respiratory tract from developing an allergic response. A team of researchers at University of Liege (Belgium), GIGA Research Center, led by Professor Fabrice Bureau, has shown that asthma is inhibited by regulatory macrophages, a cell population never previously described.
Asthma affects 6 % of the population and kills twenty thousand people in Europe each year. Patients suffering from the disease first develop, often at a very early age, a useless and even harmful immune reaction to airborne allergens (mite excrement, pet scales, pollens, etc.). Whenever exposed to these allergens, the patient's innate respiratory immune system is reactivated, thereby inducing a narrowing of the airways, which in turn results in insufficient oxygenation.
As the airborne antigens we take in with each breath are foreign to our bodies, this should elicit a response of the immune system. Moreover, ambient air contains a significant number of immunostimulatory molecules (bacterial endotoxins) that act as danger signals and should prompt the immune system to respond to the inhaled antigens. If this were so, the entire population would be asthmatic.
At GIGA Research Center (University of Liege), Fabrice Bureau and his team thus set out to understand the mechanisms which prevent the majority of the population from developing asthma and have discovered that certain cells present in the lungs are capable of inhibiting asthmatic reactions. These cells are regulatory macrophages which had not been characterized previously. The researchers have shown that these macrophages detect airborne antigens as well as concomitant immunostimulatory molecules. Furthermore, they have demonstrated that when endotoxins are present in small amounts (as is the case in ambient air), regulatory macrophages paralyse the cells of the innate respiratory immune system, thus inhibiting the development of asthma in most people. The researchers thus hypothesise that asthma can only develop when these regulatory macrophages are deficient.
"Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice", The Journal of Clinical Investigation, vol. 119, number 12, December 2009. www.jci.org
Denis Bedoret,1 Hugues Wallemacq,1 Thomas Marichal,1 Christophe Desmet,1 Florence Quesada Calvo,2 Emmanuelle Henry,3 Rodrigue Closset,1 Benjamin Dewals,4 Caroline Thielen,5 Pascal Gustin,6 Laurence de Leval,5 Nico Van Rooijen,7 Alain Le Moine,8 Alain Vanderplasschen,4 Didier Cataldo,2 Pierre-Vincent Drion,9 Muriel Moser,3 Pierre Lekeux,1 and Fabrice Bureau1
1Laboratory of Cellular and Molecular Physiology, GIGA-Research, University of Liège, Liège, Belgium.
2Laboratory of Biology of Tumors and Development, GIGA-Research, Centre Hospitalier Universitaire (CHU) de Liège, Liège, Belgium. 3Laboratory of Animal Physiology, Institute of Molecular Biology and Medicine, Université Libre de Bruxelles, Gosselies, Belgium.
4Laboratory of Immunology and Vaccinology, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
5Laboratory of Pathology, GIGA-Research, CHU de Liège, Liège, Belgium.
6Department for Functional Sciences, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
7Department of Molecular Cell Biology, Faculty of Medicine, Vrije Universiteit Medisch Centrum, Amsterdam, The Netherlands.
8Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
9Animal Facility (B23), University of Liège, Liège, Belgium.
A regulatory macrophage (in red) paralysing a cell (in blue) of the respiratory immune system. © ULg-GIGA
Pr Fabrice Bureau, Université de Liège, GIGA-Research, Laboratoire de Physiologie Cellulaire et Moléculaire, Tel +32 (0)4 366 42 84 - firstname.lastname@example.org