Progress towards new treatments for asthma
It has been known for a long time that exposure to environmental bacteria can play a protective role with regard to the later development of asthma. However, the mechanisms underpinning this theory known as the “hygiene hypothesis” remain little understood. Researchers at the University of Liege’s GIGA Research Centre offer an explanation and plan to use this discovery to implement a strategy of cellular therapy to treat asthma in humans. Their discovery has been published in the prestigious immunology journal, Immunity.
The incidence of asthma has been increasing steadily, in developed countries in particular. One of the reasons put forward to explain this epidemic is the increased level of hygiene in our environment. Indeed, epidemiological studies have shown that exposure to a “non-hygienic” environment, rich in bacteria, plays a protective role with regard to the development of allergies, including asthma. Conversely, an overly hygienic environment leads to a predisposition to asthma although the reasons for this are little-known. During allergic reactions such as asthma, our immune system does not work correctly and this leads to an exaggerated response to harmless allergens which are present in the environment (pollen, dust mites etc.). In an article published in Immunity, researchers at the University of Liege show that exposure to bacterial DNA (one of the compounds of bacteria) greatly increases a population of pulmonary macrophages and causes them to become extremely immunosuppressive resulting in the prevention and treatment of asthma in mice. This discovery offers promising possibilities for the development of cell therapy based on the administration of these regulatory macrophages to asthma patients.
Led by Professor Fabrice Bureau (Ordinary Professor at ULg and Welbio investigator - Walloon Excellence in Life Sciences and Biotechnology) and Doctor Thomas Marichal (Research associate at the F.R.S-FNRS), both of whom are researchers at ULg’s GIGA Research Centre, the team of scientists has discovered how a non-hygienic environment rich in bacterial DNA protects against asthma. In addition, synthetic compounds mimicking bacterial DNA have been tested in other studies on humans to gauge their therapeutic effect with regard to the treatment of asthma, but, up to the present, it has not been possible to put any of these compounds on the market due to issues of toxicity or due to a lack of basic knowledge about their mechanism of action. In the present case, however, the mechanisms of action have been identified and this study has resulted in a cell therapy approach which means that the use of potentially toxic compounds can be avoided.
In this study conducted on mice, researchers have firstly observed how exposure to bacterial compounds (like the compounds in the cell walls of bacteria, or even in their own DNA), or to entire bacteria, modified the lung immune environment of the lung in mice. They found that bacterial DNA, unlike the other compounds, was capable of greatly increasing a population of macrophages, called interstitial macrophages, and that this increase continued for several months in the individual.
Surprisingly, if these same macrophages are isolated from a mouse and reinjected into the lungs of a naive recipient mouse, it cannot develop asthma when exposed to dust-mite extracts. Similarly, if these macrophages are transferred to an asthmatic mouse, it becomes cured and no longer develops symptoms that are characteristic symptoms of asthma. Based on these experiments, the researchers have imagined the in vitro “manufacture” of macrophages with similar properties from monocytes, white blood cells present in human blood.
“If we succeed in creating suppressive macrophages from circulating monocytes in asthma patients, it is absolutely conceivable that we could inject these macrophages into the lungs of these same patients during a routinely-conducted bronchoscopy by the respirologists here at the Liege University Hospital, and to evaluate the therapeutic potential of these cells”, concludes Professor Fabrice Bureau.
The researchers have just filed a patent in order to protect their results and invention and they are also going to initiate clinical studies on human material.
(1) Catherine Sabatal et al, Bacterial CpG-DNA protects against asthma by expanding lung interstitial regulatory macrophages from local and splenic reservoir monocytes, Immunity (2017) DOI: http://dx.doi.org/10.1016/j.immuni.2017.02.016