GIGA-ULg researchers discovered how a non-hygienic environment, rich in bacterial DNA, helps to protect against asthma. Led by Professor Fabrice Bureau (Ordinary Professor and Welbio Investigator - Walloon Excellence in Life Sciences and Biotechnology) and Dr. Thomas Marichal (Research Associate of the F.R.S.-FNRS), the scientific team 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. The results of this study are published in Immunity.
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, 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.
Référence : 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